To see the other types of publications on this topic, follow the link: Regulation of innate immunity and inflammatory responses.
Journal articles on the topic 'Regulation of innate immunity and inflammatory responses'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'Regulation of innate immunity and inflammatory responses.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Tzeng, Hong-Tai, I.-Tsu Chyuan, and Wei-Yu Chen. "Shaping of Innate Immune Response by Fatty Acid Metabolite Palmitate." Cells 8, no. 12 (December 13, 2019): 1633. http://dx.doi.org/10.3390/cells8121633.
Full textAbstract:
Innate immune cells monitor invading pathogens and pose the first-line inflammatory response to coordinate with adaptive immunity for infection removal. Innate immunity also plays pivotal roles in injury-induced tissue remodeling and the maintenance of tissue homeostasis in physiological and pathological conditions. Lipid metabolites are emerging as the key players in the regulation of innate immune responses, and recent work has highlighted the importance of the lipid metabolite palmitate as an essential component in this regulation. Palmitate modulates innate immunity not only by regulating the activation of pattern recognition receptors in local innate immune cells, but also via coordinating immunological activity in inflammatory tissues. Moreover, protein palmitoylation controls various cellular physiological processes. Herein, we review the updated evidence that palmitate catabolism contributes to innate immune cell-mediated inflammatory processes that result in immunometabolic disorders.
2
Saitoh, Tatsuya, and Shizuo Akira. "Regulation of innate immune responses by autophagy-related proteins." Journal of Cell Biology 189, no. 6 (June 14, 2010): 925–35. http://dx.doi.org/10.1083/jcb.201002021.
Full textAbstract:
Pattern recognition receptors detect microbial components and induce innate immune responses, the first line of host defense against infectious agents. However, aberrant activation of immune responses often causes massive inflammation, leading to the development of autoimmune diseases. Therefore, both activation and inactivation of innate immune responses must be strictly controlled. Recent studies have shown that the cellular machinery associated with protein degradation, such as autophagy, is important for the regulation of innate immunity. These studies reveal that autophagy-related proteins are involved in the innate immune response and may contribute to the development of inflammatory disorders.
3
Cronkite, David Alex, and Tara M. Strutt. "The Regulation of Inflammation by Innate and Adaptive Lymphocytes." Journal of Immunology Research 2018 (June 11, 2018): 1–14. http://dx.doi.org/10.1155/2018/1467538.
Full textAbstract:
Inflammation plays an essential role in the control of pathogens and in shaping the ensuing adaptive immune responses. Traditionally, innate immunity has been described as a rapid response triggered through generic and nonspecific means that by definition lacks the ability to remember. Recently, it has become clear that some innate immune cells are epigenetically reprogrammed or “imprinted” by past experiences. These “trained” innate immune cells display altered inflammatory responses upon subsequent pathogen encounter. Remembrance of past pathogen encounters has classically been attributed to cohorts of antigen-specific memory T and B cells following the resolution of infection. During recall responses, memory T and B cells quickly respond by proliferating, producing effector cytokines, and performing various effector functions. An often-overlooked effector function of memory CD4 and CD8 T cells is the promotion of an inflammatory milieu at the initial site of infection that mirrors the primary encounter. This memory-conditioned inflammatory response, in conjunction with other secondary effector T cell functions, results in better control and more rapid resolution of both infection and the associated tissue pathology. Recent advancements in our understanding of inflammatory triggers, imprinting of the innate immune responses, and the role of T cell memory in regulating inflammation are discussed.
4
M Povroznik, Jessica, and Cory M. Robinson. "IL-27 regulation of innate immunity and control of microbial growth." Future Science OA 6, no. 7 (August 1, 2020): FSO588. http://dx.doi.org/10.2144/fsoa-2020-0032.
Full textAbstract:
IL-27 is a pleiotropic cytokine capable of influencing both innate and adaptive immune responses. With anti- and pro-inflammatory activity, IL-27 exerts its opposing effects in a cell-dependent and infectious context-specific manner. Upon pathogenic stimuli, IL-27 regulates innate immune cells, such as monocytes, dendritic cells, macrophages and neutrophils. Immune responses involving these innate cells that are negatively regulated by IL-27 signaling include inflammatory cytokine production, phagolysosomal acidification following phagocytosis, oxidative burst and autophagy. IL-27 signaling is crucial in maintaining the subtle balance between Th1 and Th2 immunity, in which protective inflammation is upregulated within the early stages of infection and subsequently downregulated once microbial growth is controlled. The immunomodulatory effects of IL-27 provide promising therapeutic targets for multiple disease types.
5
Mukherjee, S. K., A. Wilhelm, and C. G. Antoniades. "TAM receptor tyrosine kinase function and the immunopathology of liver disease." American Journal of Physiology-Gastrointestinal and Liver Physiology 310, no. 11 (June 1, 2016): G899—G905. http://dx.doi.org/10.1152/ajpgi.00382.2015.
Full textAbstract:
Tyro3, Axl, MERTK (TAM) receptor tyrosine kinases are implicated in the regulation of the innate immune response through clearance of apoptotic cellular debris and control of cytokine signaling cascades. As a result they are pivotal in regulating the inflammatory response to tissue injury. Within the liver, immune regulatory signaling is employed to prevent the overactivation of innate immunity in response to continual antigenic challenge from the gastrointestinal tract. In this review we appraise current understanding of the role of TAM receptor function in the regulation of both innate and adaptive immunity, with a focus on its impact upon hepatic inflammatory pathology.
6
Uehata, Takuya, and Osamu Takeuchi. "RNA Recognition and Immunity—Innate Immune Sensing and Its Posttranscriptional Regulation Mechanisms." Cells 9, no. 7 (July 16, 2020): 1701. http://dx.doi.org/10.3390/cells9071701.
Full textAbstract:
RNA acts as an immunostimulatory molecule in the innate immune system to activate nucleic acid sensors. It functions as an intermediate, conveying genetic information to control inflammatory responses. A key mechanism for RNA sensing is discriminating self from non-self nucleic acids to initiate antiviral responses reliably, including the expression of type I interferon (IFN) and IFN-stimulated genes. Another important aspect of the RNA-mediated inflammatory response is posttranscriptional regulation of gene expression, where RNA-binding proteins (RBPs) have essential roles in various RNA metabolisms, including splicing, nuclear export, modification, and translation and mRNA degradation. Recent evidence suggests that the control of mRNA stability is closely involved in signal transduction and orchestrates immune responses. In this study, we review the current understanding of how RNA is sensed by host RNA sensing machinery and discuss self/non-self-discrimination in innate immunity focusing on mammalian species. Finally, we discuss how posttranscriptional regulation by RBPs shape immune reactions.
7
Bickett, Thomas E., and Sana D. Karam. "Tuberculosis–Cancer Parallels in Immune Response Regulation." International Journal of Molecular Sciences 21, no. 17 (August 26, 2020): 6136. http://dx.doi.org/10.3390/ijms21176136.
Full textAbstract:
Mycobacterium tuberculosis and cancer are two diseases with proclivity for the development of resistance to the host immune system. Mechanisms behind resistance can be host derived or disease mediated, but they usually depend on the balance of pro-inflammatory to anti-inflammatory immune signals. Immunotherapies have been the focus of efforts to shift that balance and drive the response required for diseases eradication. The immune response to tuberculosis has widely been thought to be T cell dependent, with the majority of research focused on T cell responses. However, the past decade has seen greater recognition of the importance of the innate immune response, highlighting factors such as trained innate immunity and macrophage polarization to mycobacterial clearance. At the same time, there has been a renaissance of immunotherapy treatments for cancer since the first checkpoint inhibitor passed clinical trials, in addition to work highlighting the importance of innate immune responses to cancer. However, there is still much to learn about host-derived responses and the development of resistance to new cancer therapies. This review examines the similarities between the immune responses to cancer and tuberculosis with the hope that their commonalities will facilitate research collaboration and discovery.
8
Colgan, Sean P., Glenn T. Furuta, and Cormac T. Taylor. "Hypoxia and Innate Immunity: Keeping Up with the HIFsters." Annual Review of Immunology 38, no. 1 (April 26, 2020): 341–63. http://dx.doi.org/10.1146/annurev-immunol-100819-121537.
Full textAbstract:
Recent years have witnessed an emergence of interest in understanding metabolic changes associated with immune responses, termed immunometabolism. As oxygen is central to all aerobic metabolism, hypoxia is now recognized to contribute fundamentally to inflammatory and immune responses. Studies from a number of groups have implicated a prominent role for oxygen metabolism and hypoxia in innate immunity of healthy tissue (physiologic hypoxia) and during active inflammation (inflammatory hypoxia). This inflammatory hypoxia emanates from a combination of recruited inflammatory cells (e.g., neutrophils, eosinophils, and monocytes), high rates of oxidative metabolism, and the activation of multiple oxygen-consuming enzymes during inflammation. These localized shifts toward hypoxia have identified a prominent role for the transcription factor hypoxia-inducible factor (HIF) in the regulation of innate immunity. Such studies have provided new and enlightening insight into our basic understanding of immune mechanisms, and extensions of these findings have identified potential therapeutic targets. In this review, we summarize recent literature around the topic of innate immunity and mucosal hypoxia with a focus on transcriptional responses mediated by HIF.
9
Sallenave, J. M., G. A. Cunningham, R. M. James, G. McLachlan, and C. Haslett. "Regulation of Pulmonary and Systemic Bacterial Lipopolysaccharide Responses in Transgenic Mice Expressing Human Elafin." Infection and Immunity 71, no. 7 (July 2003): 3766–74. http://dx.doi.org/10.1128/iai.71.7.3766-3774.2003.
Full textAbstract:
ABSTRACT The control of lung inflammation is of paramount importance in a variety of acute pathologies, such as pneumonia, the acute respiratory distress syndrome, and sepsis. It is becoming increasingly apparent that local innate immune responses in the lung are negatively influenced by systemic inflammation. This is thought to be due to a local deficit in cytokine responses by alveolar macrophages and neutrophils following systemic bacterial infection and the development of a septic response. Recently, using an adenovirus-based strategy which overexpresses the human elastase inhibitor elafin locally in the lung, we showed that elafin is able to prime lung innate immune responses. In this study, we generated a novel transgenic mouse strain expressing human elafin and studied its response to bacterial lipopolysaccharide (LPS) when the LPS was administered locally in the lungs and systemically. When LPS was delivered to the lungs, we found that mice expressing elafin had lower serum-to-bronchoalveolar lavage ratios of proinflammatory cytokines, including tumor necrosis factor alpha (TNF-α), macrophage inflammatory protein 2, and monocyte chemoattractant protein 1, than wild-type mice. There was a concomitant increase in inflammatory cell influx, showing that there was potential priming of innate responses in the lungs. When LPS was given systemically, the mice expressing elafin had reduced levels of serum TNF-α compared to the levels in wild-type mice. These results indicate that elafin may have a dual function, promoting up-regulation of local lung innate immunity while simultaneously down-regulating potentially unwanted systemic inflammatory responses in the circulation.
10
Yao, Sheng, Shengdian Wang, Yuwen Zhu, Liqun Luo, Gefeng Zhu, Sarah Flies, Haiying Xu, et al. "PD-1 on dendritic cells impedes innate immunity against bacterial infection." Blood 113, no. 23 (June 4, 2009): 5811–18. http://dx.doi.org/10.1182/blood-2009-02-203141.
Full textAbstract:
AbstractProgrammed death one (PD-1) is an inducible molecule belonging to the immunoglobulin superfamily. It is expressed on activated T and B lymphocytes and plays pivotal roles in the negative regulation of adaptive immune responses. We report here an unexpected finding: that PD-1 could also be induced on splenic dendritic cells (DCs) by various inflammatory stimuli. Adoptive transfer of PD-1–deficient DCs demonstrates their superior capacity to wild-type DCs in innate protection of mice against lethal infection by Listeria monocytogenes. Furthermore, PD-1–deficient mice are also more resistant to the infection than wild-type controls, even in the absence of T and B cells, accompanied by elevated production of DC-derived interleukin-12 and tumor necrosis factor-α. Our results reveal a novel role of PD-1 in the negative regulation of DC function during innate immune response.
11
Mailhot, Geneviève, and John H. White. "Vitamin D and Immunity in Infants and Children." Nutrients 12, no. 5 (April 27, 2020): 1233. http://dx.doi.org/10.3390/nu12051233.
Full textAbstract:
The last couple of decades have seen an explosion in our interest and understanding of the role of vitamin D in the regulation of immunity. At the molecular level, the hormonal form of vitamin D signals through the nuclear vitamin D receptor (VDR), a ligand-regulated transcription factor. The VDR and vitamin D metabolic enzymes are expressed throughout the innate and adaptive arms of the immune system. The advent of genome-wide approaches to gene expression profiling have led to the identification of numerous VDR-regulated genes implicated in the regulation of innate and adaptive immunity. The molecular data infer that vitamin D signaling should boost innate immunity against pathogens of bacterial or viral origin. Vitamin D signaling also suppresses inflammatory immune responses that underlie autoimmunity and regulate allergic responses. These findings have been bolstered by clinical studies linking vitamin D deficiency to increased rates of infections, autoimmunity, and allergies. Our goals here are to provide an overview of the molecular basis for immune system regulation and to survey the clinical data from pediatric populations, using randomized placebo-controlled trials and meta-analyses where possible, linking vitamin D deficiency to increased rates of infections, autoimmune conditions, and allergies, and addressing the impact of supplementation on these conditions.
12
Zhang, Qian, and Xuetao Cao. "Epigenetic Remodeling in Innate Immunity and Inflammation." Annual Review of Immunology 39, no. 1 (April 26, 2021): 279–311. http://dx.doi.org/10.1146/annurev-immunol-093019-123619.
Full textAbstract:
The innate immune response is a rapid response to pathogens or danger signals. It is precisely activated not only to efficiently eliminate pathogens but also to avoid excessive inflammation and tissue damage. cis-Regulatory element–associated chromatin architecture shaped by epigenetic factors, which we define as the epiregulome, endows innate immune cells with specialized phenotypes and unique functions by establishing cell-specific gene expression patterns, and it also contributes to resolution of the inflammatory response. In this review, we focus on two aspects: ( a) how niche signals during lineage commitment or following infection and pathogenic stress program epiregulomes by regulating gene expression levels, enzymatic activities, or gene-specific targeting of chromatin modifiers and ( b) how the programed epiregulomes in turn mediate regulation of gene-specific expression, which contributes to controlling the development of innate cells, or the response to infection and inflammation, in a timely manner. We also discuss the effects of innate immunometabolic rewiring on epiregulomes and speculate on several future challenges to be encountered during the exploration of the master regulators of epiregulomes in innate immunity and inflammation.
13
Odobasic, Dragana, A. Richard Kitching, and Stephen R. Holdsworth. "Neutrophil-Mediated Regulation of Innate and Adaptive Immunity: The Role of Myeloperoxidase." Journal of Immunology Research 2016 (2016): 1–11. http://dx.doi.org/10.1155/2016/2349817.
Full textAbstract:
Neutrophils are no longer seen as leukocytes with a sole function of being the essential first responders in the removal of pathogens at sites of infection. Being armed with numerous pro- and anti-inflammatory mediators, these phagocytes can also contribute to the development of various autoimmune diseases and can positively or negatively regulate the generation of adaptive immune responses. In this review, we will discuss how myeloperoxidase, the most abundant neutrophil granule protein, plays a key role in the various functions of neutrophils in innate and adaptive immunity.
14
Li, Shuo, Xiaoli Chen, Jiafang Li, Xuejing Li, Tianxu Zhang, Gaixiang Hao, and Jinsheng Sun. "Extracellular ATP is a potent signaling molecule in the activation of the Japanese flounder (Paralichthys olivaceus) innate immune responses." Innate Immunity 26, no. 5 (January 8, 2020): 413–23. http://dx.doi.org/10.1177/1753425918804635.
Full textAbstract:
Innate immunity is the first line of defense against pathogen infections. Extracellular ATP (eATP) is one of the most studied danger-associated molecular pattern molecules that can activate host innate immune responses through binding with and activating purinergic receptors on the plasma membrane. The detailed actions of eATP on fish innate immunity, however, remain poorly understood. In this study, we investigated bacterial pathogen-induced ATP release in head kidney cells of the Japanese flounder Paralichthys olivaceus. We also examined the actions of eATP on pro-inflammatory cytokine and immune-related gene expression, the activity of induced NO synthase (iNOS), and the production of reactive oxygen species (ROS) and NO in Japanese flounder immune cells. We demonstrate that ATP is dynamically released from Japanese flounder head kidney cells into the extracellular milieu during immune challenge by formalin-inactivated Edwardsiella tarda and Vibrio anguillarum. In addition, we show that eATP administration results in profound up-regulation of pro-inflammatory cytokine gene expression, iNOS activity, and inflammatory mediator production, including ROS and NO, in Japanese flounder immune cells. Altogether, our findings demonstrate that eATP is a potent signaling molecule for the activation of innate immune responses in fish.
15
Striz, Ilja, Eva Brabcova, Libor Kolesar, and Alena Sekerkova. "Cytokine networking of innate immunity cells: a potential target of therapy." Clinical Science 126, no. 9 (January 14, 2014): 593–612. http://dx.doi.org/10.1042/cs20130497.
Full textAbstract:
Innate immune cells, particularly macrophages and epithelial cells, play a key role in multiple layers of immune responses. Alarmins and pro-inflammatory cytokines from the IL (interleukin)-1 and TNF (tumour necrosis factor) families initiate the cascade of events by inducing chemokine release from bystander cells and by the up-regulation of adhesion molecules required for transendothelial trafficking of immune cells. Furthermore, innate cytokines produced by dendritic cells, macrophages, epithelial cells and innate lymphoid cells seem to play a critical role in polarization of helper T-cell cytokine profiles into specific subsets of Th1/Th2/Th17 effector cells or regulatory T-cells. Lastly, the innate immune system down-regulates effector mechanisms and restores homoeostasis in injured tissue via cytokines from the IL-10 and TGF (transforming growth factor) families mainly released from macrophages, preferentially the M2 subset, which have a capacity to induce regulatory T-cells, inhibit the production of pro-inflammatory cytokines and induce healing of the tissue by regulating extracellular matrix protein deposition and angiogenesis. Cytokines produced by innate immune cells represent an attractive target for therapeutic intervention, and multiple molecules are currently being tested clinically in patients with inflammatory bowel disease, rheumatoid arthritis, systemic diseases, autoinflammatory syndromes, fibrosing processes or malignancies. In addition to the already widely used blockers of TNFα and the tested inhibitors of IL-1 and IL-6, multiple therapeutic molecules are currently in clinical trials targeting TNF-related molecules [APRIL (a proliferation-inducing ligand) and BAFF (B-cell-activating factor belonging to the TNF family)], chemokine receptors, IL-17, TGFβ and other cytokines.
16
Lacy, Paige, and Jennifer L. Stow. "Cytokine release from innate immune cells: association with diverse membrane trafficking pathways." Blood 118, no. 1 (July 7, 2011): 9–18. http://dx.doi.org/10.1182/blood-2010-08-265892.
Full textAbstract:
AbstractCytokines released from innate immune cells play key roles in the regulation of the immune response. These intercellular messengers are the source of soluble regulatory signals that initiate and constrain inflammatory responses to pathogens and injury. Although numerous studies describe detailed signaling pathways induced by cytokines and their specific receptors, there is little information on the mechanisms that control the release of cytokines from different cell types. Indeed, the pathways, molecules, and mechanisms of cytokine release remain a “black box” in immunology. Here, we review research findings and new approaches that have begun to generate information on cytokine trafficking and release by innate immune cells in response to inflammatory or infectious stimuli. Surprisingly complex machinery, multiple organelles, and specialized membrane domains exist in these cells to ensure the selective, temporal, and often polarized release of cytokines in innate immunity.
17
Penack, Olaf, Ernst Holler, and Marcel R. M. van den Brink. "Graft-versus-host disease: regulation by microbe-associated molecules and innate immune receptors." Blood 115, no. 10 (March 11, 2010): 1865–72. http://dx.doi.org/10.1182/blood-2009-09-242784.
Full textAbstract:
Abstract Acute graft-versus-host disease (GVHD) remains the major obstacle to a more favorable therapeutic outcome of allogeneic hematopoietic stem cell transplantation (HSCT). GVHD is characterized by tissue damage in gut, liver, and skin, caused by donor T cells that are critical for antitumor and antimicrobial immunity after HSCT. One obstacle in combating GVHD used to be the lack of understanding the molecular mechanisms that are involved in the initiation phase of this syndrome. Recent research has demonstrated that interactions between microbial-associated molecules (pathogen-associated molecular patterns [PAMPs]) and innate immune receptors (pathogen recognition receptors [PRRs]), such as NOD-like receptors (NLRs) and Toll-like receptors (TLRs), control adaptive immune responses in inflammatory disorders. Polymorphisms of the genes encoding NOD2 and TLR4 are associated with a higher incidence of GVHD in HSC transplant recipients. Interestingly, NOD2 regulates GVHD through its inhibitory effect on antigen-presenting cell (APC) function. These insights identify important mechanisms regarding the induction of GVHD through the interplay of microbial molecules and innate immunity, thus opening a new area for future therapeutic approaches. This review covers current knowledge of the role of PAMPs and PRRs in the control of adaptive immune responses during inflammatory diseases, particularly GVHD.
18
de Jonge, Wouter J. "The Gut’s Little Brain in Control of Intestinal Immunity." ISRN Gastroenterology 2013 (April 4, 2013): 1–17. http://dx.doi.org/10.1155/2013/630159.
Full textAbstract:
The gut immune system shares many mediators and receptors with the autonomic nervous system. Good examples thereof are the parasympathetic (vagal) and sympathetic neurotransmitters, for which many immune cell types in a gut context express receptors or enzymes required for their synthesis. For some of these the relevance for immune regulation has been recently defined. Earlier and more recent studies in neuroscience and immunology have indicated the anatomical and cellular basis for bidirectional interactions between the nervous and immune systems. Sympathetic immune modulation is well described earlier, and in the last decade the parasympathetic vagal nerve has been put forward as an integral part of an immune regulation network via its release of Ach, a system coined “the cholinergic anti-inflammatory reflex.” A prototypical example is the inflammatory reflex, comprised of an afferent arm that senses inflammation and an efferent arm: the cholinergic anti-inflammatory pathway, that inhibits innate immune responses. In this paper, the current understanding of how innate mucosal immunity can be influenced by the neuronal system is summarized, and cell types and receptors involved in this interaction will be highlighted. Focus will be given on the direct neuronal regulatory mechanisms, as well as current advances regarding the role of microbes in modulating communication in the gut-brain axis.
19
Karadottir, Harpa, Nikhil Nitin Kulkarni, Thorarinn Gudjonsson, Sigurbergur Karason, and Gudmundur Hrafn Gudmundsson. "Cyclic mechanical stretch down-regulates cathelicidin antimicrobial peptide expression and activates a pro-inflammatory response in human bronchial epithelial cells." PeerJ 3 (December 7, 2015): e1483. http://dx.doi.org/10.7717/peerj.1483.
Full textAbstract:
Mechanical ventilation (MV) of patients can cause damage to bronchoalveolar epithelium, leading to a sterile inflammatory response, infection and in severe cases sepsis. Limited knowledge is available on the effects of MV on the innate immune defense system in the human lung. In this study, we demonstrate that cyclic stretch of the human bronchial epithelial cell lines VA10 and BCi NS 1.1 leads to down-regulation of cathelicidin antimicrobial peptide (CAMP) gene expression. We show that treatment of VA10 cells with vitamin D3 and/or 4-phenyl butyric acid counteracted cyclic stretch mediated down-regulation ofCAMPmRNA and protein expression (LL-37). Further, we observed an increase in pro-inflammatory responses in the VA10 cell line subjected to cyclic stretch. The mRNA expression of the genes encoding pro-inflammatory cytokines IL-8 and IL-1βwas increased after cyclic stretching, where as a decrease in gene expression of chemokines IP-10 and RANTES was observed. Cyclic stretch enhanced oxidative stress in the VA10 cells. The mRNA expression of toll-like receptor (TLR)3,TLR5andTLR8was reduced, while the gene expression ofTLR2was increased in VA10 cells after cyclic stretch. In conclusion, ourin vitroresults indicate that cyclic stretch may differentially modulate innate immunity by down-regulation of antimicrobial peptide expression and increase in pro-inflammatory responses.
20
Hadjicharalambous and Lindsay. "Long Non-Coding RNAs and the Innate Immune Response." Non-Coding RNA 5, no. 2 (April 19, 2019): 34. http://dx.doi.org/10.3390/ncrna5020034.
Full textAbstract:
Innate immunity provides the initial defence against infection and it is now clear that long non-coding RNAs (lncRNAs) are important regulators of this response. Following activation of the innate response, we commonly see rapid induction of these lncRNAs and this is often mediated via the pro-inflammatory transcription factor, nuclear factor-κB (NF-κB). Knockdown studies have shown that lncRNAs tend to act in trans to regulate the expression of multiple inflammatory mediators and other responses. Mechanistically, many lncRNAs have demonstrated acting through heterogeneous nuclear ribonucleoproteins, complexes that are implicated chromatin re-modelling, transcription process and translation. In addition, these lncRNAs have also been shown to interact with multiple other proteins involved in the regulation of chromatin re-modelling, as well as those proteins involved in intracellular immune signalling, which include NF-κB. In this review, we will describe the evidence that supports this emerging role of lncRNA in the innate immune response.
21
Crifo, Bianca, and Cormac T. Taylor. "Crosstalk between toll-like receptors and hypoxia-dependent pathways in health and disease." Journal of Investigative Medicine 64, no. 2 (January 11, 2016): 369–75. http://dx.doi.org/10.1097/jim.0000000000000228.
Full textAbstract:
Toll-like receptors (TLRs) play an important role in shaping the host immune response to infection and inflammation. Tissue hypoxia is a common microenvironmental feature of infected and inflamed tissues. Furthermore, hypoxia significantly impacts the development of immune and inflammatory responses through the regulation of host innate and adaptive immunity. Here, we will discuss current knowledge in relation to the crosstalk that exists between toll-like receptor- and hypoxia-dependent signaling pathways in health and disease.
22
Hermoso, Marcela A., Tetsuya Matsuguchi, Kathleen Smoak, and John A. Cidlowski. "Glucocorticoids and Tumor Necrosis Factor Alpha Cooperatively Regulate Toll-Like Receptor 2 Gene Expression." Molecular and Cellular Biology 24, no. 11 (June 1, 2004): 4743–56. http://dx.doi.org/10.1128/mcb.24.11.4743-4756.2004.
Full textAbstract:
ABSTRACT Tumor necrosis factor alpha (TNF-α) and glucocorticoids are widely recognized as mutually antagonistic regulators of adaptive immunity and inflammation. Surprisingly, we show here that they cooperatively regulate components of innate immunity. The Toll-like receptor 2 (TLR2) gene encodes a transmembrane receptor critical for triggering innate immunity. Although TLR2 mRNA and protein are induced by inflammatory molecules such as TNF-α, we show that TLR2 is also induced by the anti-inflammatory glucocorticoids in cells where they also regulate MKP-1 mRNA and protein levels. TNF-α and glucocorticoids cooperate to regulate the TLR2 promoter, through the involvement of a 3′ NF-κB site, a STAT-binding element, and a 3′ glucocorticoid response element (GRE). Molecular studies show that the IκBα superrepressor or a STAT dominant negative element prevented TNF-α and dexamethasone stimulation of TLR2 promoter. Similarly, an AF-1 deletion mutant of glucocorticoid receptor or ablation of a putative GRE notably reduced the cooperative regulation of TLR2. Using chromatin immunoprecipitation assays, we demonstrate that all three transcription factors interact with both endogenous and transfected TLR2 promoters after stimulation by TNF-α and dexamethasone. Together, these studies define novel signaling mechanism for these three transcription factors, with a profound impact on discrimination of innate and adaptive immune responses.
23
Dommisch, Henrik, Whasun O. Chung, Maryam G. Rohani, David Williams, Minnie Rangarajan, Mike A. Curtis, and Beverly A. Dale. "Protease-Activated Receptor 2 Mediates Human Beta-Defensin 2 and CC Chemokine Ligand 20 mRNA Expression in Response to Proteases Secreted by Porphyromonas gingivalis." Infection and Immunity 75, no. 9 (June 25, 2007): 4326–33. http://dx.doi.org/10.1128/iai.00455-07.
Full textAbstract:
ABSTRACT The oral pathogen Porphyromonas gingivalis secretes proteases such as Arg-gingipain B (RgpB) that activate protease-activated receptors (PARs). Human beta-defensins (hBDs) and the macrophage inflammatory protein 3α/CC chemokine ligand 20 (CCL20) produced by epithelial cells are antimicrobial peptides that provide cytokine function and play an important role in innate immunity. The aim of the present study was to determine whether specific members of the PAR family mediate the expression of these innate immunity markers in gingival epithelial cells (GECs) when exposed to P. gingivalis cell-free culture supernatant or purified RgpB. hBD-2 mRNA in GECs was induced in response to supernatant and purified RgpB from P. gingivalis (P = 0.02 and P = 0.016, respectively). This effect was abrogated by the protease inhibitor tosyl-l-lysine chloromethyl ketone (TLCK) (P < 0.05). In response to P. gingivalis supernatant and to purified RgpB, the hBD-2 mRNA expression was significantly decreased in PAR-2 gene knockdown cells, whereas no change was detected in PAR-1 gene knockdown cells. CCL20 mRNA expression also increased in response to the supernatant of P. gingivalis, and this effect was blocked by the protease inhibitor, TLCK (P = 0.05 and P = 0.024, respectively), and was blocked in PAR-2 gene knockdown cells. Our data indicate that hBD-2 and CCL20 mRNA up-regulation by P. gingivalis supernatant and purified RgpB was mediated via PAR-2, but not via PAR-1, and that proteases play a role in the regulation of innate immune responses in GECs. GECs use PARs to recognize P. gingivalis and mediate cell responses involved in innate immunity.
24
Chieosilapatham, Panjit, Shigaku Ikeda, Hideoki Ogawa, and Francois Niyonsaba. "Tissue-specific Regulation of Innate Immune Responses by Human Cathelicidin LL-37." Current Pharmaceutical Design 24, no. 10 (May 28, 2018): 1079–91. http://dx.doi.org/10.2174/1381612824666180327113418.
Full textAbstract:
Cathelicidins form one of the major families of antimicrobial peptides and have been identified in many vertebrates, including humans. LL-37, the only human member of the cathelicidin family, is detected in most sites of the human body that is normally exposed to microbes, including the epithelial lining of the skin, gastrointestinal tract, genitourinary tract and lungs. This peptide is also expressed by a variety of epithelial cells and immune cells, such as neutrophils, monocytes and mast cells. LL-37 has emerged as a key component of innate immunity due to its direct antimicrobial activity against a broad spectrum of invading pathogens. It also exhibits diverse immunomodulatory functions by activating both pro- and anti-inflammatory mediators; inducing cell migration, proliferation and differentiation; and regulating apoptosis of epithelial cells and neutrophils. Given that the phenotypic and functional properties of immune compartments are different and significantly impacted by the anatomical sites, tissue-specific factors of host origin and microbial communities play important roles in the regulation of LL-37. This review summarizes the expression and biological functions of LL-37 and discusses its significant roles in the innate immune system based on its anatomical distribution.
25
Xie, Na, and Gang Liu. "ncRNA-regulated immune response and its role in inflammatory lung diseases." American Journal of Physiology-Lung Cellular and Molecular Physiology 309, no. 10 (November 15, 2015): L1076—L1087. http://dx.doi.org/10.1152/ajplung.00286.2015.
Full textAbstract:
Despite the greatly expanded knowledge on the regulation of immune response by protein molecules, there is increasing understanding that noncoding RNAs (ncRNAs) are also an integral component of this regulatory network. Abnormal immune response serves a central role in the initiation, progression, and exacerbation of inflammatory lung diseases, such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, and acute respiratory distress syndrome/acute lung injury. Dysregulation of ncRNAs has been linked to various immunopathologies. In this review, we highlighted the role of ncRNAs in the regulation of innate and adaptive immunity and summarized recent findings that ncRNAs participate in the pathogenesis of inflammatory lung diseases via their regulation of pulmonary immunity. We also discussed therapeutic potentials for targeting ncRNAs to treat these lung disorders.
26
Nedoszytko, Bogusław, Edyta Reszka, Danuta Gutowska-Owsiak, Magdalena Trzeciak, Magdalena Lange, Justyna Jarczak, Marek Niedoszytko, et al. "Genetic and Epigenetic Aspects of Atopic Dermatitis." International Journal of Molecular Sciences 21, no. 18 (September 4, 2020): 6484. http://dx.doi.org/10.3390/ijms21186484.
Full textAbstract:
Atopic dermatitis is a heterogeneous disease, in which the pathogenesis is associated with mutations in genes encoding epidermal structural proteins, barrier enzymes, and their inhibitors; the role of genes regulating innate and adaptive immune responses and environmental factors inducing the disease is also noted. Recent studies point to the key role of epigenetic changes in the development of the disease. Epigenetic modifications are mainly mediated by DNA methylation, histone acetylation, and the action of specific non-coding RNAs. It has been documented that the profile of epigenetic changes in patients with atopic dermatitis (AD) differs from that observed in healthy people. This applies to the genes affecting the regulation of immune response and inflammatory processes, e.g., both affecting Th1 bias and promoting Th2 responses and the genes of innate immunity, as well as those encoding the structural proteins of the epidermis. Understanding of the epigenetic alterations is therefore pivotal to both create new molecular classifications of atopic dermatitis and to enable the development of personalized treatment strategies.
27
Rodríguez-Cerdeira, C., A. Lopez-Bárcenas, B. Sánchez-Blanco, and R. Arenas. "The Role of IL-33 in Host Response toCandida albicans." Scientific World Journal 2014 (2014): 1–7. http://dx.doi.org/10.1155/2014/340690.
Full textAbstract:
Background. Interleukin (IL) 33 is a recently identified pleiotropic cytokine that influences the activity of multiple cell types and orchestrates complex innate and adaptive immune responses.Methods. We performed an extensive review of the literature published between 2005 and 2013 on IL-33 and related cytokines, their functions, and their regulation of the immune system followingCandida albicanscolonization. Our literature review included cross-references from retrieved articles and specific data from our own studies.Results. IL-33 (IL-1F11) is a recently identified member of the IL-1 family of cytokines. Accumulating evidence suggests a pivotal role of the IL-33/ST2 axis in host immune defense against fungal pathogens, includingC. albicans. IL-33 induces a Th2-type inflammatory response and activates both innate and adaptive immunity. Studies in animal models have shown that Th2 inflammatory responses have a beneficial role in immunity against gastrointestinal and systemic infections byCandidaspp.Conclusions. This review summarizes the most important clinical studies and case reports describing the beneficial role of IL-33 in immunity and host defense mechanisms against pathogenic fungi. The finding that the IL-33/ST2 axis is involved in therapeutic target has implications for the prevention and treatment of inflammatory diseases, including acute or chronic candidiasis.
28
Wenzel, Ulrich O., Marlies Bode, Jörg Köhl, and Heimo Ehmke. "A pathogenic role of complement in arterial hypertension and hypertensive end organ damage." American Journal of Physiology-Heart and Circulatory Physiology 312, no. 3 (March 1, 2017): H349—H354. http://dx.doi.org/10.1152/ajpheart.00759.2016.
Full textAbstract:
The self-amplifying cascade of messenger and effector molecules of the complement system serves as a powerful danger-sensing system that protects the host from a hostile microbial environment, while maintaining proper tissue and organ function through effective clearance of altered or dying cells. As an important effector arm of innate immunity, it also plays important roles in the regulation of adaptive immunity. Innate and adaptive immune responses have been identified as crucial players in the pathogenesis of arterial hypertension and hypertensive end organ damage. In line with this view, complement activation may drive the pathology of hypertension and hypertensive injury through its impact on innate and adaptive immune responses. It is well known that complement activation can cause tissue inflammation and injury and complement-inhibitory drugs are effective treatments for several inflammatory diseases. In addition to these proinflammatory properties, complement cleavage fragments of C3 and C5 can exert anti-inflammatory effects that dampen the inflammatory response to injury. Recent experimental data strongly support a role for complement in arterial hypertension. The remarkably similar clinical and histopathological features of malignant nephrosclerosis and atypical hemolytic uremic syndrome, which is driven by complement activation, suggest a role for complement also in the development of malignant nephrosclerosis. Herein, we will review canonical and noncanonical pathways of complement activation as the framework to understand the multiple roles of complement in arterial hypertension and hypertensive end organ damage.
29
Lang, Roland, and Faizal Raffi. "Dual-Specificity Phosphatases in Immunity and Infection: An Update." International Journal of Molecular Sciences 20, no. 11 (June 2, 2019): 2710. http://dx.doi.org/10.3390/ijms20112710.
Full textAbstract:
Kinase activation and phosphorylation cascades are key to initiate immune cell activation in response to recognition of antigen and sensing of microbial danger. However, for balanced and controlled immune responses, the intensity and duration of phospho-signaling has to be regulated. The dual-specificity phosphatase (DUSP) gene family has many members that are differentially expressed in resting and activated immune cells. Here, we review the progress made in the field of DUSP gene function in regulation of the immune system during the last decade. Studies in knockout mice have confirmed the essential functions of several DUSP-MAPK phosphatases (DUSP-MKP) in controlling inflammatory and anti-microbial immune responses and support the concept that individual DUSP-MKP shape and determine the outcome of innate immune responses due to context-dependent expression and selective inhibition of different mitogen-activated protein kinases (MAPK). In addition to the canonical DUSP-MKP, several small-size atypical DUSP proteins regulate immune cells and are therefore also reviewed here. Unexpected and complex findings in DUSP knockout mice pose new questions regarding cell type-specific and redundant functions. Another emerging question concerns the interaction of DUSP-MKP with non-MAPK binding partners and substrate proteins. Finally, the pharmacological targeting of DUSPs is desirable to modulate immune and inflammatory responses.
30
Edelson, Brian T., Thomas P. Stricker, Zhengzhi Li, S. Kent Dickeson, Virginia L. Shepherd, Samuel A. Santoro, and Mary M. Zutter. "Novel collectin/C1q receptor mediates mast cell activation and innate immunity." Blood 107, no. 1 (January 1, 2006): 143–50. http://dx.doi.org/10.1182/blood-2005-06-2218.
Full textAbstract:
Abstract Mast cells play a critical role in innate immunity, allergy, and autoimmune diseases. The receptor/ligand interactions that mediate mast cell activation are poorly defined. The α2β1 integrin, a receptor for collagens, laminins, decorin, E-cadherin, matrix metalloproteinase-1 (MMP-1), endorepellin, and several viruses, has been implicated in normal developmental, inflammatory, and oncogenic processes. We recently reported that α2 integrin subunit–deficient mice exhibited markedly diminished neutrophil and IL-6 responses during Listeria monocytogenes–and zymosan-induced peritonitis. Peritoneal mast cells require α2β1 integrin expression for activation in response to pathogens, yet the ligand and molecular mechanisms by which the α2β1 integrin induces activation and cytokine secretion remain unknown. We now report that the α2β1 integrin is a novel receptor for multiple collectins and the C1q complement protein. We demonstrate that the α2β1 integrin provides a costimulatory function required for mast cell activation and cytokine secretion. This finding suggests that the α2β1 integrin is not only important for innate immunity but may serve as a critical target for the regulation of autoimmune/allergic disorders.
31
Schmidt, Eric P., Warren L. Lee, Rachel L. Zemans, Cory Yamashita, and Gregory P. Downey. "On, Around, and Through: Neutrophil-Endothelial Interactions in Innate Immunity." Physiology 26, no. 5 (October 2011): 334–47. http://dx.doi.org/10.1152/physiol.00011.2011.
Full textAbstract:
This manuscript will review our current understanding of neutrophilic polymorphonuclear leukocyte (neutrophil) interactions with the endothelium during immune and inflammatory responses, focusing on the molecular mechanisms regulating neutrophil adhesion to and migration through the endothelium in response to infection or tissue injury. This is a complex and dynamic area of research and one that has been the topic of several recent comprehensive reviews to which the interested reader is referred ( 64 , 118 , 131 ). By design, this review will begin with a brief review of some basic aspects of neutrophil biology and endothelial adhesion to provide a foundation. The remainder of the review will focus on selected areas of this complex field, specifically the role of the endothelial glycocalyx in regulating neutrophil adhesion and the mechanisms and consequences of migration of neutrophils between (paracellular) and through (transcellular) endothelial cells during egress from the vasculature.
32
Schweitzer, Katrin, and Michael Naumann. "Control of NF-κB activation by the COP9 signalosome." Biochemical Society Transactions 38, no. 1 (January 19, 2010): 156–61. http://dx.doi.org/10.1042/bst0380156.
Full textAbstract:
The transcription factor NF-κB (nuclear factor κB) exerts crucial functions in the regulation of innate and adaptive immune responses, wound healing and tissue maintenance and in the development of immune cells. Tight control of NF-κB is essential for an efficient defence against pathogens and environmental stress to protect organisms from inflammatory diseases including cancer. An involvement of the CSN (COP9 signalosome) in the regulation of NF-κB has been discovered recently. The CSN is a conserved multiprotein complex, which mainly functions in the control of proteolysis. Here, we review recent observations indicating important roles of the CSN in the control of NF-κB in innate immunity, as well as T-cell activation and maturation.
33
Zernecke, Alma. "MicroRNAs in the regulation of immune cell functions – implications for atherosclerotic vascular disease." Thrombosis and Haemostasis 107, no. 04 (2012): 626–33. http://dx.doi.org/10.1160/th11-08-0603.
Full textAbstract:
SummaryRegarded as a chronic inflammatory disease of the vessel wall, the development of atherosclerotic lesions is shaped by immune responses and their regulation. Macrophages and dendritic cells are positioned at the crossroad of innate and adaptive immune responses by sensing atherogenic danger signals and by taking up and presenting antigens. T helper cells and auto-antibodies produced by B cells, together with their cytokine responses in turn modulate atheroprogression. In addition, platelets contribute to atherosclerosis by multiple pathways. microRNAs (miRNAs) that post-transcriptionally regulate gene expression may thus critically control immune cell differentiation and functions during plaque evolution. This review summarises the role of miRNAs in regulating lipid uptake and expression of inflammatory mediators in monocytes/macrophages and dendritic cells, in lymphocyte functions with a focus on T helper cell responses, as well as in platelet biology, and the implications of altering these functions in vascular pathology and atherosclerosis. T systematically survey miRNA functions in controlling molecular mechanisms and immune responses in atherosclerosis holds potential for the development of novel miRNA-based strategies for therapies targeting inflammation and immunity in atherosclerosis.
34
Sun, Lizhe, Xiaofeng Yang, Zuyi Yuan, and Hong Wang. "Metabolic Reprogramming in Immune Response and Tissue Inflammation." Arteriosclerosis, Thrombosis, and Vascular Biology 40, no. 9 (September 2020): 1990–2001. http://dx.doi.org/10.1161/atvbaha.120.314037.
Full textAbstract:
Innate and adaptive immunity participate in and regulate numerous human diseases. Increasing evidence implies that metabolic reprogramming mediates immune cell functional changes during immune responses. In this review, we present and discuss our current understanding of metabolic regulation in different immune cells and their subsets in response to pathological stimuli. An interactive biochemical and molecular model was established to characterize metabolic reprogramming and their functional implication in anti-inflammatory, immune resolution, and proinflammatory responses. We summarize 2 major features of metabolic reprogramming in inflammatory stages in innate and adaptive immune cells: (1) energy production and biosynthesis reprogramming, including increased glycolysis and decreased oxidative phosphorylation, to secure faster ATP production and biosynthesis for defense response and damage repair and (2) epigenetic reprogramming, including enhanced histone acetylation and suppressed DNA methylation, due to altered accessibility of acetyl/methyl group donor and metabolite-modulated enzymatic activity. Finally, we discuss current strategies of metabolic and epigenetic therapy in cardiovascular disease and recommend cell-specific metabolic and gene-targeted site-specific epigenetic alterations for future therapies.
35
Ting, Jenny P.-Y. "The NLR (NBD-LRR containing) Family of Intracellular Sensors in Inflammation and Immune Response." Blood 114, no. 22 (November 20, 2009): SCI—22—SCI—22. http://dx.doi.org/10.1182/blood.v114.22.sci-22.sci-22.
Full textAbstract:
Abstract Abstract SCI-22 The NLR gene family encodes proteins that are comprised of conserved nucleotide-binding domain (NBD) and leucine rich-repeats (LRR). These genes are conserved from plants, lower animals to mammals. Family members include CIITA, NOD1, NOD2, and NLRP3. Several of these genes are genetically linked to immunodeficiency, inflammatory and immune diseases. This large gene family controls a number of innate responses, including inflammasome function leading to IL-1b/IL-18 production, cell death and type I IFN production. This talk will discuss the broad function of this family of genes, with emphasis on their regulation of inflammation and innate immunity, and their divergent roles in pathogen responses. Disclosures No relevant conflicts of interest to declare.
36
Hiemstra, P. S. "Defensins and cathelicidins in inflammatory lung disease: beyond antimicrobial activity." Biochemical Society Transactions 34, no. 2 (March 20, 2006): 276–78. http://dx.doi.org/10.1042/bst0340276.
Full textAbstract:
Innate immunity provides an effective first line of defence against infections. This is of particular importance in the lung, an organ that is exposed to a large number of pathogens that are inhaled. Antimicrobial peptides play an important role in the defence against these pathogens as effector molecules of innate immunity. These peptides are mainly produced by phagocytes and epithelial cells, and kill a wide range of micro-organisms: Gram-negative and Gram-positive bacteria, fungi and (enveloped) viruses. However, it is increasingly evident that these peptides not only act as endogenous antibiotics, but also display a range of other functions, including activities that are involved in regulating immune responses and inflammation, and wound repair. In this review, these activities are highlighted and their role in inflammatory lung disorders is discussed.
37
Brown, Eric M., Douglas J. Kenny, and Ramnik J. Xavier. "Gut Microbiota Regulation of T Cells During Inflammation and Autoimmunity." Annual Review of Immunology 37, no. 1 (April 26, 2019): 599–624. http://dx.doi.org/10.1146/annurev-immunol-042718-041841.
Full textAbstract:
The intestinal microbiota plays a crucial role in influencing the development of host immunity, and in turn the immune system also acts to regulate the microbiota through intestinal barrier maintenance and immune exclusion. Normally, these interactions are homeostatic, tightly controlled, and organized by both innate and adaptive immune responses. However, a combination of environmental exposures and genetic defects can result in a break in tolerance and intestinal homeostasis. The outcomes of these interactions at the mucosal interface have broad, systemic effects on host immunity and the development of chronic inflammatory or autoimmune disease. The underlying mechanisms and pathways the microbiota can utilize to regulate these diseases are just starting to emerge. Here, we discuss the recent evidence in this area describing the impact of microbiota-immune interactions during inflammation and autoimmunity, with a focus on barrier function and CD4+ T cell regulation.
38
Zhang, Xinhua, Yuko Kimura, Chongyun Fang, Lin Zhou, Georgia Sfyroera, John D. Lambris, Rick A. Wetsel, Takashi Miwa, and Wen-Chao Song. "Regulation of Toll-like receptor–mediated inflammatory response by complement in vivo." Blood 110, no. 1 (July 1, 2007): 228–36. http://dx.doi.org/10.1182/blood-2006-12-063636.
Full textAbstract:
Toll-like receptors (TLRs) and complement are 2 components of innate immunity that are critical for first-line host defense and elicitation of adaptive immune responses. Many pathogen-associated molecular patterns activate both TLR and complement, but whether and how these 2 systems, when coactivated in vivo, interact with each other has not been well studied. We demonstrate here a widespread regulation of TLR signaling by complement in vivo. The TLR ligands lipopolysacharride (TLR4), zymosan (TLR2/6), and CpG oligonucleotide (TLR9) caused, in a complement-dependent manner, strikingly elevated plasma interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), and IL-1β, and/or decreased plasma IL-12 levels in mice deficient in the membrane complement inhibitor decay-accelerating factor (DAF). A similar outcome was observed in wild-type mice cotreated with the TLR ligands and cobra venom factor, a potent complement activator. The regulatory effect of complement on TLR-induced cytokine production in vivo was mediated by the anaphylatoxin receptors C5aR and C3aR. Additionally, changes in lipopolysaccharide (LPS)–induced cytokine production in DAF-deficient mice correlated with increased mitogen-activated protein kinase and nuclear factor-κB activation in the spleen. These results reveal a strong interaction between complement and TLR signaling in vivo and suggest a novel mechanism by which complement promotes inflammation and modulates adaptive immunity.
39
Chen, Zhangbo, Shijun Wang, Lingyun Li, Zhong Huang, and Ke Ma. "Anti-Inflammatory Effect of IL-37-Producing T-Cell Population in DSS-Induced Chronic Inflammatory Bowel Disease in Mice." International Journal of Molecular Sciences 19, no. 12 (December 5, 2018): 3884. http://dx.doi.org/10.3390/ijms19123884.
Full textAbstract:
Inflammatory bowel disease (IBD) is a chronic inflammatory disease that is thought to arise in part from abnormal adaptive immune responses against intestinal microbiota. T lymphocytes play significant roles in triggering mucosal inflammation and/or maintaining gut immune homeostasis. It has been demonstrated that IL-37 expresses in a variety of cells and exerts a protective function involved in both innate immunity and adaptive immunity. In the present study, a population of IL-37-producing T-cells was detected in the spleen and mesenteric lymph nodes (MLNs) in IL-37+/+ mice after dextran sodium sulfate (DSS) induction. Adoptive transfer of the T-cells from the spleen of IL-37+/+ mice following DSS treatment partly recovered the body weight, improved the disease activity index (DAI) and macroscopic damage score, and attenuated the intestinal inflammation. In addition, colon shortening, an indirect marker of inflammation, was decreased, consistent with the decreased IFN-γ level and the increased IL-10 level in the colonic tissue. Collectively, our data uncovered a subset of T-lymphocytes expressing IL-37, which represents a potent regulation of immunity and serves as the protective role in chronic IBD.
40
Richards, Carl D., Laura Izakelian, Anisha Dubey, Grace Zhang, Steven Wong, Karen Kwofie, Aatif Qureshi, and Fernando Botelho. "Regulation of IL-33 by Oncostatin M in Mouse Lung Epithelial Cells." Mediators of Inflammation 2016 (2016): 1–12. http://dx.doi.org/10.1155/2016/9858374.
Full textAbstract:
IL-33 modulates both innate and adaptive immune responses at tissue sites including lung and may play critical roles in inflammatory lung disease. Although IL-33 expression can be altered upon NF-Kappa B activation, here we examine regulation by Oncostatin M, a gp130 cytokine family member, in mouse lung tissue. Responses were assessed in BALB/c mouse lung at day 7 of transient overexpression using endotracheally administered adenovirus encoding OSM (AdOSM) or empty vector (AdDel70). Whole lung extracts showed induction of IL-33 mRNA (>20-fold) and protein (10-fold increase in immunoblots) by AdOSM relative to AdDel70. Immunohistochemistry for IL-33 indicated a marked induction of nuclear staining in alveolar epithelial cellsin vivo. Oncostatin M stimulated IL-33 mRNA and IL-33 full length protein in C10 mouse type 2 alveolar epithelial cells in culture in time-dependent and dose-dependent fashion, whereas IL-6, LIF, IL-31, IL-4, or IL-13 did not, and TGFβrepressed IL-33. IL-33 induction was associated with activation of STAT3, and pharmacological inhibition of STAT3 ameliorated IL-33 levels. These results indicate Oncostatin M as a potent inducer of IL-33 in mouse lung epithelial cells and suggest that an OSM/IL-33 axis may participate in innate immunity and inflammatory conditions in lung.
41
Nuriev, Rinat, and Cecilia Johansson. "Chemokine regulation of inflammation during respiratory syncytial virus infection." F1000Research 8 (October 31, 2019): 1837. http://dx.doi.org/10.12688/f1000research.20061.1.
Full textAbstract:
Respiratory syncytial virus (RSV) can cause severe lower respiratory tract infections especially in infants, immunocompromised individuals and the elderly and is the most common cause of infant hospitalisation in the developed world. The immune responses against RSV are crucial for viral control and clearance but, if dysregulated, can also result in immunopathology and impaired gas exchange. Lung immunity to RSV and other respiratory viruses begins with the recruitment of immune cells from the bloodstream into the lungs. This inflammatory process is controlled largely by chemokines, which are small proteins that are produced in response to innate immune detection of the virus or the infection process. These chemokines serve as chemoattractants for granulocytes, monocytes, lymphocytes and other leukocytes. In this review, we highlight recent advances in the field of RSV infection and disease, focusing on how chemokines regulate virus-induced inflammation.
42
Ear, Thornin, Olga Tatsiy, Frédérick L. Allard, and Patrick P. McDonald. "Regulation of Discrete Functional Responses by Syk and Src Family Tyrosine Kinases in Human Neutrophils." Journal of Immunology Research 2017 (2017): 1–7. http://dx.doi.org/10.1155/2017/4347121.
Full textAbstract:
Neutrophils play a critical role in innate immunity and also influence adaptive immune responses. This occurs in good part through their production of inflammatory and immunomodulatory cytokines, in conjunction with their prolonged survival at inflamed foci. While a picture of the signaling machinery underlying these neutrophil responses is now emerging, much remains to be uncovered. In this study, we report that neutrophils constitutively express various Src family isoforms (STKs), as well as Syk, and that inhibition of these protein tyrosine kinases selectively hinders inflammatory cytokine generation by acting posttranscriptionally. Accordingly, STK or Syk inhibition decreases the phosphorylation of signaling intermediates (e.g., eIF-4E, S6K, and MNK1) involved in translational control. By contrast, delayed apoptosis appears to be independent of either STKs or Syk. Our data therefore significantly extend our understanding of which neutrophil responses are governed by STKs and Syk and pinpoint some signaling intermediates that are likely involved. In view of the foremost role of neutrophils in several chronic inflammatory conditions, our findings identify potential molecular targets that could be exploited for future therapeutic intervention.
43
Missiroli, Sonia, Ilaria Genovese, Mariasole Perrone, Bianca Vezzani, Veronica A. M. Vitto, and Carlotta Giorgi. "The Role of Mitochondria in Inflammation: From Cancer to Neurodegenerative Disorders." Journal of Clinical Medicine 9, no. 3 (March 9, 2020): 740. http://dx.doi.org/10.3390/jcm9030740.
Full textAbstract:
The main features that are commonly attributed to mitochondria consist of the regulation of cell proliferation, ATP generation, cell death and metabolism. However, recent scientific advances reveal that the intrinsic dynamicity of the mitochondrial compartment also plays a central role in proinflammatory signaling, identifying these organelles as a central platform for the control of innate immunity and the inflammatory response. Thus, mitochondrial dysfunctions have been related to severe chronic inflammatory disorders. Strategies aimed at reestablishing normal mitochondrial physiology could represent both preventive and therapeutic interventions for various pathologies related to exacerbated inflammation. Here, we explore the current understanding of the intricate interplay between mitochondria and the innate immune response in specific inflammatory diseases, such as neurological disorders and cancer.
44
Chiba, Tomoki, Hidetoshi Inoko, Minoru Kimura, and Takehito Sato. "Role of nuclear IκBs in inflammation regulation." BioMolecular Concepts 4, no. 2 (April 1, 2013): 187–96. http://dx.doi.org/10.1515/bmc-2012-0039.
Full textAbstract:
AbstractA wide variety of environmental cues, including inflammatory cytokines, ligands for pattern recognition receptors and endogenous danger signals, activate the inducible transcription factor nuclear factor-κB (NF-κB), which is a central regulator of inflammatory and immune responses. Excessive activation of NF-κB results in the development of severe diseases, such as chronic inflammatory disorders, autoimmune diseases and cancer. Therefore, the transcriptional activity of NF-κB is tightly regulated at multiple steps. One mechanism is mediated by the inhibitor of κB (IκB), a well-defined regulator of NF-κB that resides in the cytoplasm and prevents NF-κB from nuclear entry by sequestration. Recently, several atypical IκBs that reside in the nucleus were identified: Bcl-3, IκBζ, IκBNS and IκBη. In contrast to conventional IκBs, these atypical IκBs positively and negatively modulate NF-κB-mediated transcription. The function of atypical IκBs is independent of the prevention of NF-κB nuclear entry. Therefore, atypical IκBs are considered distinct from conventional IκBs and have been termed ‘nuclear IκBs.’ In addition to these members, our recent study indicated that IκBL, originally reported as a susceptibility gene for rheumatoid arthritis, also serves as a nuclear IκB. Biological and genetic studies strongly suggest that nuclear IκBs play important roles in the pathogenesis of inflammatory and autoimmune diseases via the regulation of both innate and adaptive immunity. In this review, we discuss the recent advances in our understanding of nuclear IκBs in the context of NF-κB-mediated transcriptional regulation and inflammatory responses.
45
Foka, Pelagia, Alexios Dimitriadis, Eirini Karamichali, Emmanouil Kochlios, Petros Eliadis, Vaia Valiakou, John Koskinas, Avgi Mamalaki, and Urania Georgopoulou. "HCV-Induced Immunometabolic Crosstalk in a Triple-Cell Co-Culture Model Capable of Simulating Systemic Iron Homeostasis." Cells 10, no. 9 (August 30, 2021): 2251. http://dx.doi.org/10.3390/cells10092251.
Full textAbstract:
Iron is crucial to the regulation of the host innate immune system and the outcome of many infections. Hepatitis C virus (HCV), one of the major viral human pathogens that depends on iron to complete its life cycle, is highly skilled in evading the immune system. This study presents the construction and validation of a physiologically relevant triple-cell co-culture model that was used to investigate the input of iron in HCV infection and the interplay between HCV, iron, and determinants of host innate immunity. We recorded the expression patterns of key proteins of iron homeostasis involved in iron import, export and storage and examined their relation to the iron regulatory hormone hepcidin in hepatocytes, enterocytes and macrophages in the presence and absence of HCV. We then assessed the transcriptional profiles of pro-inflammatory cytokines Interleukin-6 (IL-6) and interleukin-15 (IL-15) and anti-inflammatory interleukin-10 (IL-10) under normal or iron-depleted conditions and determined how these were affected by infection. Our data suggest the presence of a link between iron homeostasis and innate immunity unfolding among liver, intestine, and macrophages, which could participate in the deregulation of innate immune responses observed in early HCV infection. Coupled with iron-assisted enhanced viral propagation, such a mechanism may be important for the establishment of viral persistence and the ensuing chronic liver disease.
46
Yu, Jiabo, Xiang Sun, Jian Yi Gerald Goie, and Yongliang Zhang. "Regulation of Host Immune Responses against Influenza A Virus Infection by Mitogen-Activated Protein Kinases (MAPKs)." Microorganisms 8, no. 7 (July 17, 2020): 1067. http://dx.doi.org/10.3390/microorganisms8071067.
Full textAbstract:
Influenza is a major respiratory viral disease caused by infections from the influenza A virus (IAV) that persists across various seasonal outbreaks globally each year. Host immune response is a key factor determining disease severity of influenza infection, presenting an attractive target for the development of novel therapies for treatments. Among the multiple signal transduction pathways regulating the host immune activation and function in response to IAV infections, the mitogen-activated protein kinase (MAPK) pathways are important signalling axes, downstream of various pattern recognition receptors (PRRs), activated by IAVs that regulate various cellular processes in immune cells of both innate and adaptive immunity. Moreover, aberrant MAPK activation underpins overexuberant production of inflammatory mediators, promoting the development of the “cytokine storm”, a characteristic of severe respiratory viral diseases. Therefore, elucidation of the regulatory roles of MAPK in immune responses against IAVs is not only essential for understanding the pathogenesis of severe influenza, but also critical for developing MAPK-dependent therapies for treatment of respiratory viral diseases. In this review, we will summarise the current understanding of MAPK functions in both innate and adaptive immune response against IAVs and discuss their contributions towards the cytokine storm caused by highly pathogenic influenza viruses.
47
Eo, Seong Kug, Sujin Lee, Sangjun Chun, and Barry T. Rouse. "Modulation of Immunity against Herpes Simplex Virus Infection via Mucosal Genetic Transfer of Plasmid DNA Encoding Chemokines." Journal of Virology 75, no. 2 (January 15, 2001): 569–78. http://dx.doi.org/10.1128/jvi.75.2.569-578.2001.
Full textAbstract:
ABSTRACT In this study, we examined the effects of murine chemokine DNA, as genetic adjuvants given mucosally, on the systemic and distal mucosal immune responses to plasmid DNA encoding gB of herpes simplex virus (HSV) by using the mouse model. The CC chemokines macrophage inflammatory protein 1β (MIP-1β) and monocyte chemotactic protein 1 (MCP-1) biased the immunity to the Th2-type pattern as judged by the ratio of immunoglobulin isotypes and interleukin-4 cytokine levels produced by CD4+ T cells. The CXC chemokine MIP-2 and the CC chemokine MIP-1α, however, mounted immune responses of the Th1-type pattern, and such a response rendered recipients more resistant to HSV vaginal infection. In addition, MIP-1α appeared to act via the upregulation of antigen-presenting cell (APC) function and the expression of costimulatory molecules (B7-1 and B7-2), whereas MIP-2 enhanced Th1-type CD4+ T-cell-mediated adaptive immunity by increasing gamma interferon secretion from activated NK cells. Our results emphasize the value of using the mucosal route to administer DNA modulators such as chemokines that function as adjuvants by regulating the activity of innate immunity. Our findings provide new insight into the value of CXC and CC chemokines, which act on different innate cellular components as the linkage signals between innate and adaptive immunity in mucosal DNA vaccination.
48
Thiagarajah, Jay R., Jeffrey Chang, Jeremy A. Goettel, Alan S. Verkman, and Wayne I. Lencer. "Aquaporin-3 mediates hydrogen peroxide-dependent responses to environmental stress in colonic epithelia." Proceedings of the National Academy of Sciences 114, no. 3 (January 3, 2017): 568–73. http://dx.doi.org/10.1073/pnas.1612921114.
Full textAbstract:
The colonic epithelium provides an essential barrier against the environment that is critical for protecting the body and controlling inflammation. In response to injury or gut microbes, colonic epithelial cells produce extracellular hydrogen peroxide (H2O2), which acts as a potent signaling molecule affecting barrier function and host defense. In humans, impaired regulation of H2O2 in the intestine has been associated with early-onset inflammatory bowel disease and colon cancer. Here, we show that signal transduction by H2O2 depends on entry into the cell by transit through aquaporin-3 (AQP3), a plasma membrane H2O2-conducting channel. In response to injury, AQP3-depleted colonic epithelial cells showed defective lamellipodia, focal adhesions, and repair after wounding, along with impaired H2O2 responses after exposure to the intestinal pathogen Citrobacter rodentium. Correspondingly, AQP3−/− mice showed impaired healing of superficial wounds in the colon and impaired mucosal innate immune responses against C. rodentium infection, manifested by reduced crypt hyperplasia, reduced epithelial expression of IL-6 and TNF-α, and impaired bacterial clearance. These results elucidate the signaling mechanism of extracellular H2O2 in the colonic epithelium and implicate AQP3 in innate immunity at mucosal surfaces.
49
Zhang, Yiting, Chao Li, Siyi Li, Yiping Lu, Sitong Du, Xinning Zeng, Xi Chen, and Jie Chen. "Dihydrotanshinone I Alleviates Crystalline Silica-Induced Pulmonary Inflammation by Regulation of the Th Immune Response and Inhibition of STAT1/STAT3." Mediators of Inflammation 2019 (July 9, 2019): 1–15. http://dx.doi.org/10.1155/2019/3427053.
Full textAbstract:
Occupational exposure to crystalline silica (CS) results in a persistent pulmonary inflammatory response that eventually leads to abnormal tissue repair, disability, and death. The inflammatory-immune responses occur in the early stages of CS exposure, and both innate and adaptive immunity are involved. CD4+ T cells play a pivotal role in the pathogenesis of CS-induced pulmonary disease, which has no proven curative therapy. Dihydrotanshinone I (DHI), a natural product isolated from Salvia miltiorrhiza Bunge (Danshen), has anti-inflammatory and immunomodulatory properties. However, whether DHI has a protective effect on CS-induced lung disease, how it influences the Th immune response, and the potential underlying molecular mechanism(s) have not been fully clarified. In this study, DHI treatment of CS-exposed mice reduced the expression of proinflammatory cytokines and the infiltration of immune cells. It significantly ameliorated CS-induced pulmonary inflammation by attenuating T helper (Th)1 and Th17 responses, which were tightly related to the inhibition of STAT1 and STAT3. DHI significantly altered Th2 cytokines but not the Th2 nuclear transcription factor. Furthermore, our study found that DHI treatment also affected regulatory T cell activity in CS-injured mice. Taken together, our findings indicated that DHI could modulate Th responses and alleviate CS-induced pulmonary inflammation, suggesting a novel application of DHI in CS-induced pulmonary disease.
50
Huang, F. C., and S. C. Huang. "The different effects of probiotics treatment on Salmonella-induced interleukin-8 response in intestinal epithelia cells via PI3K/Akt and NOD2 expression." Beneficial Microbes 7, no. 5 (November 30, 2016): 739–48. http://dx.doi.org/10.3920/bm2015.0181.
Full textAbstract:
Salmonella spp. remains a major public health problem for the whole world. Intestinal epithelial cells serve as an essential component of the innate mucosal immune system to defend against Salmonella infection. A substantial amount of evidence has accumulated that probiotics can regulate interleukin 8 (IL-8) involved in innate immunity. However, the exact effect of probiotics on epithelial IL-8 response to Salmonella infection is not well understood. Therefore, we investigated the action of probiotics on Salmonella-infected Caco-2 cells and its novel mechanisms. Two probiotic strains were examined for Salmonella-induced IL-8 responses and regulating proteins using Caco-2 cell cultures. We demonstrated probiotic, either Lactobacillus rhamnosus GG or Bifidobacterium animalis subsp. lactis DSM10140, administered before Salmonella infection conferred significantly suppressive effect on Salmonella-induced IL-8 responses in Caco-2 cells, either in secreted protein or mRNA, via the PI3K/Akt signal pathway while probiotic administered after infection enhanced Salmonella-induced IL-8 responses via nucleotide-binding oligomerisation domain-containing protein 2 expression in membrane. These findings suggest that the different regulation of probiotics on Salmonella-induced IL-8 responses in Caco-2 cells according to the administered timing supports a rationale for the therapeutic use of probiotics in the treatment of Salmonella colitis and inflammatory bowel disease. This can explain the reported controversial effect of probiotics on these diseases.