Academic literature on the topic 'Lipoxine A4'
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Journal articles on the topic "Lipoxine A4"
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Busija, D. W., W. Armstead, C. W. Leffler, and R. Mirro. "Lipoxins A4 and B4 dilate cerebral arterioles of newborn pigs." American Journal of Physiology-Heart and Circulatory Physiology 256, no. 2 (February 1, 1989): H468—H471. http://dx.doi.org/10.1152/ajpheart.1989.256.2.h468.
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We determined the effects of lipoxins A4 and B4 on the cerebral microcirculation of neonatal pigs and whether vascular responses were modulated by prostanoids. Pial arteriolar diameters were determined using a closed cranial window and intravital microscopy. Before lipoxin A4 application, arteriolar diameter was 143 +/- 6 microns (means +/- SE). Topical application of lipoxin A4 increased the diameter to 160 +/- 7 microns at 0.1 ng/ml, 167 +/- 7 microns at 1 ng/ml, and 173 +/- 7 microns at 10 ng/ml (n = 9). Before application of lipoxin B4, arteriolar diameter was 146 +/- 7 microns. Topical application of lipoxin B4 increased the diameter to 165 +/- 7, 169 +/- 6, and 175 +/- 6 microns at 0.1, 1, and 10 ng/ml (n = 9), respectively. Intravenous injection of indomethacin (5 mg/kg) or vehicle did not affect these responses. Levels of prostaglandins E2 and F2 alpha in cerebrospinal fluid (measured by radioimmunoassay) did not increase in response to lipoxins. We conclude that lipoxins are dilator stimuli in the cerebral circulation and that prostanoids do not mediate these responses.
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Chandrasekharan, Jayashree A., Xiao M. Huang, Alexander C. Hwang, and Neelam Sharma-Walia. "Altering the Anti-inflammatory Lipoxin Microenvironment: a New Insight into Kaposi's Sarcoma-Associated Herpesvirus Pathogenesis." Journal of Virology 90, no. 24 (September 28, 2016): 11020–31. http://dx.doi.org/10.1128/jvi.01491-16.
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ABSTRACTLipoxins are host anti-inflammatory molecules that play a vital role in restoring tissue homeostasis. The efficacy of lipoxins and their analog epilipoxins in treating inflammation and its associated diseases has been well documented. Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL) are two well-known inflammation related diseases caused by Kaposi's sarcoma-associated herpesvirus (KSHV). Controlling inflammation is one of the strategies adopted to treat KS and PEL, a primary motivation for exploring and evaluating the therapeutic potential of using lipoxins. This study documents how KSHV manipulates and downregulates the secretion of the anti-inflammatory lipoxin A4 in host cells and the viral factors involved in this process usingin vitroKS and PEL cells as models. The presence of the lipoxin A4 receptor/formyl peptidyl receptor (ALX/FPR) in KS patient tissue sections andin vitroKS and PEL cell models offers a novel possibility for treating KS and PEL with lipoxins. Treatingde novoKSHV-infected endothelial cells with lipoxin and epilipoxin creates an anti-inflammatory environment by decreasing the levels of NF-κB, AKT, ERK1/2, COX-2, and 5-lipoxygenase. Lipoxin treatment on CRISPR/CAS9 technology-mediated ALX/FPR gene deletion revealed the importance of the lipoxin receptor ALX for effective lipoxin signaling. A viral microRNA (miRNA) cluster was identified as the primary factor contributing to the downregulation of lipoxin A4 secretion in host cells. The KSHV miRNA cluster probably targets enzyme 15-lipoxygenase, which is involved in lipoxin A4 synthesis. This study provides a new insight into the potential treatment of KS and PEL using nature's own anti-inflammatory molecule, lipoxin.IMPORTANCEKSHV infection has been shown to upregulate several host proinflammatory factors, which aid in its survival and pathogenesis. The influence of KSHV infection on anti-inflammatory molecules is not well studied. Since current treatment methods for KS and PEL are fraught with unwanted side effects and low efficiency, the search for new therapeutics is therefore imperative. The use of nature's own molecule lipoxin as a drug is promising. This study opens up new domains in KSHV research focusing on how the virus modulates lipoxin secretion and warrants further investigation of the therapeutic potential of lipoxin usingin vitrocell models for KS and PEL.
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Tułowiecka, Nikola, Dariusz Kotlęga, Andrzej Bohatyrewicz, and Małgorzata Szczuko. "Could Lipoxins Represent a New Standard in Ischemic Stroke Treatment?" International Journal of Molecular Sciences 22, no. 8 (April 19, 2021): 4207. http://dx.doi.org/10.3390/ijms22084207.
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Introduction: Cardiovascular diseases including stroke are one of the most common causes of death. Their main cause is atherosclerosis and chronic inflammation in the body. An ischemic stroke may occur as a result of the rupture of unstable atherosclerotic plaque. Cardiovascular diseases are associated with uncontrolled inflammation. The inflammatory reaction produces chemical mediators that stimulate the resolution of inflammation. One of these mediators is lipoxins—pro-resolving mediators that are derived from the omega-6 fatty acid family, promoting inflammation relief and supporting tissue regeneration. Aim: The aim of the study was to review the available literature on the therapeutic potential of lipoxins in the context of ischemic stroke. Material and Methods: Articles published up to 31 January 2021 were included in the review. The literature was searched on the basis of PubMed and Embase in terms of the entries: ‘stroke and lipoxin’ and ‘stroke and atherosclerosis’, resulting in over 110 articles in total. Studies that were not in full-text English, letters to the editor, and conference abstracts were excluded. Results: In animal studies, the injection/administration of lipoxin A4 improved the integrity of the blood–brain barrier (BBB), decreased the volume of damage caused by ischemic stroke, and decreased brain edema. In addition, lipoxin A4 inhibited the infiltration of neutrophils and the production of cytokines and pro-inflammatory chemokines, such as interleukin (Il-1β, Il-6, Il-8) and tumor necrosis factor-α (TNF-α). The beneficial effects were also observed after introducing the administration of lipoxin A4 analog—BML-111. BML-111 significantly reduces the size of a stroke and protects the cerebral cortex, possibly by reducing the permeability of the blood–brain barrier. Moreover, more potent than lipoxin A4, it has an anti-inflammatory effect by inhibiting the production of pro-inflammatory cytokines and increasing the amount of anti-inflammatory cytokines. Conclusions: Lipoxins and their analogues may find application in reducing damage caused by stroke and improving the prognosis of patients after ischemic stroke.
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Chiron, R., Y. Grumbach, Nga Vuthi Quynh, V. Verriere, and V. Urbach. "116 Influence de l’antibiothérapie sur le taux d’IL-8 et de Lipoxine A4 dans les expectorations des patients atteints de mucoviscidose." Revue des Maladies Respiratoires 23, no. 5 (November 2006): 573. http://dx.doi.org/10.1016/s0761-8425(06)71944-1.
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Svensson, Camilla I., Michela Zattoni, and Charles N. Serhan. "Lipoxins and aspirin-triggered lipoxin inhibit inflammatory pain processing." Journal of Experimental Medicine 204, no. 2 (January 22, 2007): 245–52. http://dx.doi.org/10.1084/jem.20061826.
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Inflammatory conditions can lead to debilitating and persistent pain. This hyperalgesia reflects sensitization of peripheral terminals and facilitation of pain signaling at the spinal level. Studies of peripheral systems show that tissue injury triggers not only inflammation but also a well-orchestrated series of events that leads to reversal of the inflammatory state. In this regard, lipoxins represent a unique class of lipid mediators that promote resolution of inflammation. The antiinflammatory role of peripheral lipoxins raises the hypothesis that similar neuraxial systems may also down-regulate injury-induced spinal facilitation of pain processing. We report that the lipoxin A4 receptor is expressed on spinal astrocytes both in vivo and in vitro and that spinal delivery of lipoxin A4, as well as stable analogues, attenuates inflammation-induced pain. Furthermore, activation of extracellular signal-regulated kinase and c-Jun N-terminal kinase in astrocytes, which has been indicated to play an important role in spinal pain processing, was attenuated in the presence of lipoxins. This linkage opens the possibility that lipoxins regulate spinal nociceptive processing though their actions upon astrocytic activation. Targeting mechanisms that counterregulate the spinal consequences of persistent peripheral inflammation provide a novel endogenous mechanism by which chronic pain may be controlled.
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Grumbach, Y., N. Vu Thi Quynh, and V. Urbach. "095 Effet de la lipoxine A4 sur l’expression de la zonula-occludens-1 et la formation des jonctions serrées dans l’épithelium bronchique." Revue des Maladies Respiratoires 23, no. 5 (November 2006): 562. http://dx.doi.org/10.1016/s0761-8425(06)71923-4.
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Romano, M., X. S. Chen, Y. Takahashi, S. Yamamoto, C. D. Funk, and C. N. Serhan. "Lipoxin synthase activity of human platelet 12-lipoxygenase." Biochemical Journal 296, no. 1 (November 15, 1993): 127–33. http://dx.doi.org/10.1042/bj2960127.
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Human platelets and megacaryocytes generate lipoxins from exogenous leukotriene A4 (LTA4). We examined the role of human 12-lipoxygenase (12-LO) in lipoxin generation with recombinant histidine-tagged human platelet enzyme (6His-12-LO), partially purified 12-LO from human platelets (HPL 12-LO) and, for the purposes of direct comparison, permeabilized platelets. Recombinant and HPL 12-LO catalysed the conversion of intact LTA4 into both lipoxin A4 (LXA4) and lipoxin B4 (LXB4). In contrast, only negligible quantities of LXA4 were generated when recombinant 12-LO was incubated with the non-enzymic hydrolysis products of LTA4.6His-12-LO also converted a non-allylic epoxide, 5(6)-epoxy-(8Z,11Z,14Z)-eicosatrienoic acid. The apparent Km and Vmax. for lipoxin synthase activity of 6His-12-LO were estimated to be 7.9 +/- 0.8 microM and 24.5 +/- 2.5 nmol/min per mg respectively, and the LXB4 synthase activity of this enzyme was selectively regulated by suicide inactivation. Aspirin gave a 2-fold increase in lipoxin formation by platelets but did not enhance the conversion of LTA4 by the recombinant 12-LO. These results provide direct evidence for LXA4 and LXB4 synthase activity of human platelet 12-LO. Moreover, they suggest that 12-LO is a dual-function enzyme that carries both oxygenase and lipoxin synthase activity.
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Tarannum, Fouzia, and Mohamed Faizuddin. "Effect of Alox-15 Polymorphism on GCF Levels of Lipoxin-A4 in Chronic Periodontitis: A Preliminary Study." Brazilian Dental Journal 28, no. 2 (April 2017): 140–47. http://dx.doi.org/10.1590/0103-6440201701094.
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Lipoxins play an important role in periodontal resolution, hence, investigation of genetic polymorphism of lipoxin gene may provide important information on the role of lipoxins in periodontal disease pathogenesis. The aim of this study was to investigate a polymorphism of C-to-T substitution at position c.-292 in ALOX15 (reticulocyte-type 15 lipoxygenase 1) gene in patients with chronic periodontitis and to associate the polymorphism with gingival crevicular fluid (GCF) lipoxin A4 (LXA4) levels. Forty-five chronic periodontitis and 45 periodontally healthy patients were included in this case-control study. Plaque index, calculus index, sulcus bleeding index, full mouth probing depth (PD) and clinical attachment loss (CAL) were recorded. GCF and blood samples were collected. GCF was analyzed for LXA4 levels by enzyme linked immunosorbant assay. Genotyping of ALOX15 polymorphism was studied using PCR. Mean LXA4 was lower in periodontitis group compared to the periodontally healthy group. There was a negative correlation between CAL and LXA4. The CC genotype was higher in the study group than in the control group. In the study group, mean CAL was significantly lower among individuals with the CT genotype. Mean LXA4 was significantly lower in CC genotype (45.0±7.11 ng/mL) compared to CT genotype (50.81±5.81 ng/mL) among the patients with periodontitis. The results suggest that LXA4 and c.-292T allele are associated with periodontal health. Polymorphisms in the ALOX15 gene may influence periodontal disease pathogenesis. Hence, investigation of such polymorphisms could benefit the evaluation of lipoxins role in periodontal disease.
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Yu, Suhui, Jianming Xie, Yukai Xiang, Shengjie Dai, Dinglai Yu, Hongwei Sun, Bicheng Chen, and Mengtao Zhou. "Downregulation of TNF-α/TNF-R1 Signals by AT-Lipoxin A4 May Be a Significant Mechanism of Attenuation in SAP-Associated Lung Injury." Mediators of Inflammation 2019 (April 11, 2019): 1–13. http://dx.doi.org/10.1155/2019/9019404.
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Our previous studies verified the potent anti-inflammatory effects against severe acute pancreatitis (SAP) of AT-Lipoxin A4 and their analogues. However, the anti-inflammatory effects of AT-Lipoxin A4 on SAP-associated lung injury are not thoroughly known. We used western blot, polymerase chain reaction (PCR), and immunofluorescence to investigate the downregulation of TNF-α signals in cellular and animal models of SAP-associated lung injury following AT-Lipoxin A4 intervention. In vitro, we found that AT-Lipoxin A4 markedly suppressed protein expression in TNF-α signals in human pulmonary microvascular endothelial cell, such as tumor necrosis factor receptor-associated factor 2 (TRAF2), TNF-R1-associated death domain (TRADD), receptor-interacting protein (RIP), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. Moreover, AT-Lipoxin A4 inhibited downstream signals activated by TNF-α, including NF-κB/p65, JNK/MAPK, and ERK/MAPK. In vivo, AT-Lipoxin A4 significantly decreased pathological scores of the pancreas and lungs and the serum levels of IL-6 and TNF-α. Immunofluorescence, western blotting, and real-time PCR assay showed that AT-Lipoxin A4 significantly attenuated the expression of TNF-R1, TRADD, TRAF2, and RIP in the lungs of SAP rats. In addition, the activation of NF-κB was also downregulated by AT-Lipoxin A4 administration as compared with SAP rats. AT-Lipoxin A4 could inhibit the production of proinflammatory mediators and activation of TNF-α downstream signals such as NF-κB and MAPK. Downregulation of TNF-α signals by AT-Lipoxin A4 may be a significant mechanism in the attenuation of SAP-associated lung injury.
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Katoh, T., K. Takahashi, D. K. DeBoer, C. N. Serhan, and K. F. Badr. "Renal hemodynamic actions of lipoxins in rats: a comparative physiological study." American Journal of Physiology-Renal Physiology 263, no. 3 (September 1, 1992): F436—F442. http://dx.doi.org/10.1152/ajprenal.1992.263.3.f436.
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Interactions between either the arachidonate 5-lipoxygenase (5-LO) and 15-LO or 5-LO and 12-LO can lead to the formation of lipoxins. Although the functional significance of lipoxygenase products of arachidonic acid has been recognized increasingly in glomerular inflammation, less is known regarding the specific effects of lipoxins on renal hemodynamics. Here, we examine the renal actions of lipoxin (LX) A4, LXB4, and, the recently identified 7-cis-11-trans-LXA4, which were administered into the renal artery of the euvolemic male Munich-Wistar rat. LXA4 caused increases in renal plasma flow (RPF) and glomerular filtration rate (GFR) in a dose-dependent manner. These effects were reversed during cyclooxygenase inhibition. LXB4 decreased both RPF and GFR, and its mode of action was independent of cyclooxygenase activity. 7-cis-11-trans-LXA4 decreased RPF and GFR, which effects were abolished during systemic infusion of the leukotriene D4 receptor antagonist SKF 104353. Results indicate that each of these lipoxins displays distinct hemodynamic effects via a specific mode of action on the renal vasculature of rats. Moreover, they suggest mechanisms whereby lipoxins may participate in the changes of renal hemodynamics that occur during glomerular inflammatory processes.
Dissertations / Theses on the topic "Lipoxine A4"
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Grumbach, Yaël. "Effet de la lipoxine A4 sur l'épithélium bronchique humain." Montpellier 2, 2007. http://www.theses.fr/2007MON20074.
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Verrière, Valia. "Effet des glucocorticoïdes et de la lipoxine A4 sur l'épithélium bronchique humain : rôle du calcium et du pH intracellulaires." Montpellier 2, 2007. http://www.theses.fr/2007MON20044.
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Barnig, Cindy. "Rôle des éosinophiles et des cellules lymphoïdes innées dans l'asthme." Thesis, Strasbourg, 2014. http://www.theses.fr/2014STRAJ028.
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Dans la première partie de cette thèse, nous avons cherché à déterminer le rôle de l’éosinophile circulant dans l’asthme par une approche transcriptomique. Nos résultats suggèrent que l’éosinophile recruté sur un site inflammatoire présente des fonctions immunomodulatrices, importantes dans la réparation tissulaire et le retour à l’homéostasie. Dans la deuxième partie de cette thèse, nous avons étudié le rôle des cellules NK et des cellules lymphoïdes innées de type 2 (ILC2) dans l’inflammation asthmatique. Les cellules NK circulantes sont fortement activées dans l’asthme sévère et ont la capacité d’induire l’apoptose d’éosinophiles autologues in vitro. La PGD2 induit la production d’IL-13 par les ILC2 en synergie avec les cytokines épithéliales IL-25 et IL-33. Enfin, ces fonctions sont régulées par la LXA4. En conclusion, notre travail de thèse met en lumière de nouveaux rôles pour l’éosinophile et les cellules lymphoïdes innées dans l’immunopathologie de l’asthmeIn the first part of the thesis, we adopted a transcriptomic-based approach to investigate the activation state of circulating eosinophils in patients with asthma and other unrelated hypereosinophilic diseases. Taken together, our results, which suggest that esoinophils, recruited to inflammatory sites exhibit non-specific immunomodulatory functions important for tissue repair and homeostasis. In the second part of the thesis, we investigated the role of NK cells and type 2 innate lymphoid cells (ILC2) in asthma inflammation. Circulating NK cells are highly activated in severe asthma and promote apoptosis of autologous eosinophils in vitro. ILC2 generate interleukin-13 in response to prostaglandin D2 alone and in a synergistic manner with the airway epithelial cytokines IL-25 and IL-33. Finally, these functions are regulated by lipoxine A4. In conclusion, this thesis highlights new roles for eosinophils and innate lymphoid cells in asthma immunopathology
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Pamplona, Fabrício Alano. "Lipoxina A4." reponame:Repositório Institucional da UFSC, 2012. http://repositorio.ufsc.br/xmlui/handle/123456789/93851.
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Tese (doutorado) - Universidade Federal de Santa Catarina, Centro de Ciênicas Biológicas, Programa de Pós-Graduação em Farmacologia, Florianópolis, 2010Made available in DSpace on 2012-10-25T04:00:48Z (GMT). No. of bitstreams: 1 277593.pdf: 2618597 bytes, checksum: 32488c4ad5d58474bd92bce7d89cae69 (MD5)
Lipoxinas e endocanabinóides são eicosanóides endógenos que são liberados sob demanda em resposta à estimulação neuronal ou injúria tecidual. A lipoxina A4 (LXA4) ativa receptores ALX e exerce importante papel na resolução de processos inflamatórios, mas informações a respeito dos seus efeitos no sistema nervoso central são escassas. As evidências disponíveis até o momento sugerem que a LXA4 pode influenciar a atividade cerebral de uma maneira similar aos canabinóides. Endocanabinóides como a anandamida (AEA) e o 2-araquidonilglicerol (2-AG) exercem diversos efeitos centrais por ativação dos receptores canabinóides CB1. Apesar dos endocanabinóides e lipoxinas compartilharem similaridades estruturais e funcionais, ainda não há descrição de sua relação farmacológica. Desta maneira, o objetivo deste trabalho foi investigar a participação do sistema endocanabinóide nos efeitos centrais da LXA4. Camundongos Swiss albinos foram injetados i.c.v. com LXA4 (0,01-1 pmol / 5l) ou controle e 5 min depois avaliados no teste da tétrade canabinóide (catalepsia, locomoção, analgesia e temperatura retal), considerado preditivo para atividade canabimimética. A investigação destas respostas prosseguiu com a injeção do antagonista canabinóide CB1 SR141716A (1 mg/kg, i.p.) ou do antagonista de receptores ALX BOC-2 (10 g/kg, i.p.) 50 min antes da injeção i.c.v. de LXA4 (1 pmol / 5 l). A participação dos receptores CB1 nos efeitos da LXA4 foi confirmada em camundongos knockout para receptores CB1. A interação farmacológica entre LXA4 e os endocanabinóides foi abordada pela co-injeção de doses sub-efetivas de AEA (10 pmol/ 2 l) ou 2-AG (1 pmol/ 2 l) e LXA4 (0,01 pmol/ 2 l). A ligação da LXA4 (1 nM # 10 M) nos receptores canabinóides CB1 receptores foi avaliada no ensaio competitivo de ligação contra o [3H]SR141716A em membranas de cérebro de camundongos, na presença e ausência de AEA (1 nM # 10 M). Possíveis efeitos da LXA4 na degradação dos endocanabinóides foram testados em ensaios in vitro das respectivas enzimas de degradação para a AEA e o 2-AG. Além do mais, nós testamos se a 15-epi-LXA4, uma lipoxina liberada por ação da aspirina, também exerce atividade canabimimética como a LXA4 de ocorrência natural. LXA4 (0,1 - 1 pmol) induziu catalepsia, hipolocomoção, analgesia e hipotermia nos camundongos. Estes efeitos foram antagonizados pelo antagonista dos receptores canabinóides CB1 SR141716A, mas não pelo antagonista dos receptores ALX BOC-2, além de não ocorreram em camundongos knockout para os receptores XV CB1. A LXA4 potencializou a catalepsia induzida pela AEA, mas não pelo 2-AG. A LXA4 praticamente não inibiu a ligação do [3H]SR141716A às membranas de cérebro de camundongos, mas aumentou a inibição causada pela AEA. Não houve efeito da LXA4 sobre a atividade das enzimas de degradação de endocanabinóides FAAH e MAGL (até 10 M). A aspirina potencializou os efeitos da AEA de uma maneira dependente da enzima 5-LOX e dos receptores CB1, provavelmente porque a 15-epi-LXA4 também influencia a afinidade da AEA pelos receptores CB1. Os presentes resultados sugerem que a LXA4 exerce efeitos centrais via receptores CB1 interagindo positivamente com o endocanabinóide AEA. Apesar da LXA4 não influenciar o metabolismo de endocanabinóides, este trabalho traz evidências de que a LXA4 aumenta a afinidade da AEA pelos receptores CB1 por um mecanismo de modulação alostérica positiva. Esta é certamente uma descoberta pioneira na farmacologia do sistema endocabinóide.
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Bedi, Pallavi. "Lipoxin A4 on neutrophil reprogramming in bronchiectasis." Thesis, University of Edinburgh, 2018. http://hdl.handle.net/1842/31210.
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Introduction: Bronchiectasis is a common chronic debilitating respiratory condition. Patients suffer daily cough, excess sputum production and recurrent chest infections because of inflamed and permanently damaged airways. The pathogenesis of bronchiectasis is poorly understood. Pulmonary pathology shows excess neutrophilic airways inflammation, but despite this over two thirds of patients are chronically infected with potential pathogenic microorganisms. The acute inflammatory response is a protective mechanism that is evolved to eliminate invading organisms and should ideally be self-limiting and lead to complete resolution. The driver for persistent neutrophilic airway inflammation in bronchiectasis is unknown, but infection is considered to play a major role. AIMS The main aims of this thesis were to: (i) Characterize neutrophils in the serum and airways in bronchiectasis in the stable state and during exacerbations; (ii) Cohort study to establish if LXA4 deficiency correlates with disease severity (iii) Characterize lipids in bronchiectasis airways and peripheral blood to establish the correlation of LXA4 to disease severity; (iv) To investigate a potential mechanism for low levels of LXA4 in bronchiectasis, lipoxin biosynthetic genes expression will be measured; (v) Assess the anti-inflammatory and pro resolution effect of LXA4 on neutrophils and monocyte derived macrophages from healthy volunteers; (vi) Assess the anti-inflammatory and pro resolution effect of LXA4 on neutrophils during exacerbations in bronchiectasis and community acquired pneumonia. Methods (I) To establish the serum neutrophil subtype in stable state and following antibiotic treatment in patients with bronchiectasis, the following studies were done. Inclusion criteria: Patients aged 18-80 were recruited. All had an established radiological diagnosis of bronchiectasis (CT of the chest). Patients had clinically significant bronchiectasis, aetiology being either idiopathic or post infection. Exclusion Criteria: current smokers or ex-smokers of less than 1 year; >20 pack year history; cystic fibrosis; active allergic bronchopulmonary aspergillosis; active tuberculosis; poorly controlled asthma; severe COPD requiring nebulised bronchodilators or long term oxygen therapy; patients on aspirin or leukotriene inhibitors, pregnancy or breast feeding, active malignancy. A. 6 patients with mild bronchiectasis, 6 patients with severe bronchiectasis and 6 healthy volunteers were recruited. Serum and airways neutrophils were subsequently isolated. Neutrophil apoptosis, CD11b and CD62L expression, myeloperoxidase release, superoxide generation, phagocytosis and killing of GFP labeled bacteria were assessed. B. To compare serum with airways neutrophils function, bacterial phagocytosis and killing of GFP labeled bacteria was done, with both serum and airways neutrophils. Samples were obtained from the above group of patients. C. To establish neutrophil function following antibiotic treatment, 6 bronchiectasis patients at the beginning (day1) and the end (day14) of intravenous antibiotic therapy for an exacerbation were studied. As a control group, 6 community acquired pneumonia patients at the beginning (day1) and the end (day 5) of intravenous antibiotic therapy for infection were studied. Induced sputum and peripheral blood was taken at day1 and 5, where able. Phagocytosis and killing of GFP labeled bacteria was assessed and the two groups compared. (II) To address if lipoxin A4 deficiency correlates with disease severity, a cohort study was done in bronchiectasis patients. 169 patients were recruited and followed up for 1 year. Assessments done were Bronchiectasis severity index, systemic inflammatory markers (white cell count, ESR and c-reactive protein), Forced Expired Volume in 1sec, Forced Vital Capacity and its ratio, antibiotic courses in 1 year, hospital admissions in 1 year, sputum microbiology, quality of life assessments by Leicester Cough Questionnaire and St. Georges Respiratory Questionnaire, interleukin 8, myeloperoxidase, neutrophil elastase and leukotriene B4 (from sputum). (III) To assess effect of lipoxin on disease severity, 6 healthy volunteers, 10 patients with mild disease, 15 with moderate and 9 with severe disease were recruited. Disease severity was calculated as per the bronchiectasis severity index. All participants had 60mls of blood taken and underwent a bronchoscopy. Two segments of the lungs were washed out from bronchiectasis patients, an area affected by bronchiectasis and an area unaffected by bronchiectasis. This led to patients acting as their own internal control. Serum and airways neutrophils (from both segments) were subsequently isolated. Assessments done were systemic inflammatory markers (white cell count, ESR and c-reactive protein), serum lipoxin A4 and the cathelicidin LL-37, Forced Expired Volume in 1sec, Forced Vital Capacity and its ratio, transfer factor for carbon monoxide, antibiotic courses in 1 year, hospital admissions in 1 year and sputum microbiology. Phagocytosis and bacterial killing were assessed by both serum and airways neutrophils. From bronchoalveolar lavage fluid (BALF), I measured myeloperoxidase and neutrophil elastase. For both serum and BALF, lipidomics were obtained. (IV) To address the impact of anatomic compartment, gene expression was measured in from endobronchial brushings from the same cohort of bronchiectasis patients and controls as above, where samples were available. qPCR was performed for the following eicosanoid biosynthetic genes- 5 Lipoxygenase (LOX), 15 LO-A, 15LO-B and leukotriene (LT) A4 hydrolase. (V) To assess the anti inflammatory and pro resolution effect of LXA4 on neutrophils and monocyte derived macrophages from healthy volunteers, freshly isolated PMN will be treated with LXA4 or vehicle control. Spontaneous apoptosis was measured. fMLF and cytochalasin B was added and the inflammatory response assessed measuring myeloperoxidase (MPO), free neutrophil elastase (NE), CD11b, CD18 and CD62L. Human monocytes and PMNs were isolated from bronchiectasis patients. Following differentiation, LXA4 treated or control adherent, washed MDMs will be incubated with apoptotic stained PMNs. Efferocytosis was analyzed by flow cytometry. (VI) To establish the effect of Lipoxin A4 on neutrophil function following antibiotic treatment, the same study group used to evaluate aim 1 was taken. As a control group, 6 community acquired pneumonia patients at the beginning (day1) and the end (day 5) of oral or intravenous antibiotic therapy for infection were studied. Induced sputum and peripheral blood was taken at day1 and 5, where able. Phagocytosis and killing of GFP labeled bacteria and the effect of Lipoxin A4 was assessed and the two groups compared. Serum and sputum lipidomics were obtained in bronchiectasis exacerbations on day 1 and day 14. Serum lipidomics was obtained in pneumonia on day 1 and day 5. RESULTS (I) Neutrophil sub type study (Studied on healthy volunteers/ mild/ severe bronchiectasis) Peripheral blood neutrophils from bronchiectasis patients showed that there was significantly more viable neutrophils in mild and severe bronchiectasis compared to healthy volunteers, p=0.002 and p=0.005 respectively. In addition, there was significantly less apoptotic neutrophils in mild and severe bronchiectasis compared to healthy volunteers, p=0.0003 and p < 0.0001 respectively. There was a significantly higher level of CD11b in the mild (p=0.01) and severe bronchiectasis (p=0.01) compared to healthy volunteers. There was more CD62L shedding (p=0.02) and myeloperoxidase release (p=0.04) in bronchiectasis compared to healthy volunteers. There was lesser phagocytosis in mild (p=0.04) and severe (p=0.03) bronchiectasis compared to healthy volunteers. This led to lesser bacterial killing in mild (p=0.04) and severe (p=0.0004) bronchiectasis compared to healthy volunteers.
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Varanasi, Srinivas. "Effect of lipoxin A4 and prostaglandin E2 on bone healing /." [St. Lucia, Qld.], 2005. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe18967.pdf.
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Sordi, Regina de. "Papel dual da lipoxina A4, nas alterações inflamatórias e cardiovasculares na sepse." reponame:Repositório Institucional da UFSC, 2013. https://repositorio.ufsc.br/handle/123456789/107088.
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Tese (doutorado) - Universidade Federal de Santa Catarina, Centro de Ciências Biológicas, Programa de Pós-Graduação em Farmacologia, Florianópolis, 2013.Made available in DSpace on 2013-12-05T23:10:56Z (GMT). No. of bitstreams: 1 318109.pdf: 5339491 bytes, checksum: 3bd18f691339280cf25525f6dcba51e8 (MD5) Previous issue date: 2013
A pneumonia é uma das principais causas de sepse, que por sua vez é a maior causa de morte nas Unidades de Terapia Intensiva, mesmo com os recentes avanços da medicina. O estudo da sepse e de novas alternativas terapêuticas permanecem um desafio devido à complexidade desta síndrome, cujo principal componente é uma resposta inflamatória desordenada. A lipoxina A4 (LXA4) é um mediador lipídico endógeno com potentes ações anti-inflamatórias e pró-resolutivas, entretanto seu papel em processos infecciosos como a sepse ainda não é bem entendido. Portanto, o objetivo do presente trabalho foi avançar no entendimento do papel da LXA4 e do seu receptor FPR2/ALX na resposta inflamatória desordenada que ocorre no modelo de sepse induzida por pneumonia. Para isso, a sepse foi induzida em camundongos Swiss machos pela inoculação intratraqueal de Klebsiella pneumoniae. Os parâmetros inflamatórios e cardiovasculares foram avaliados 6, 24 e 48 h após a infecção. Os resultados mostram que a severidade da infecção e a mortalidade dos animais se correlacionam com a quantidade de bactéria inoculada. Os animais sépticos apresentaram alterações histopatológicas nos pulmões, exibiram aumento do número de células no lavado bronco-alveolar e dos níveis das citocinas pró-inflamatórias TNF-? e IL-1? local e sistemicamente, desenvolveram leucopenia, além de hipotensão e hiporreatividade a agentes vasoconstritores. Além do pulmão, foram encontradas bactérias no baço e coração dos animais, indicando disseminação da infecção. Interessantemente, houve aumento da expressão da NOS-2 em tempos mais tardios, enquanto que os níveis da NOS-1 e NOS-3 permaneceram inalterados. A maior expressão da NOS-2 coincidiu com uma grande produção de NO no foco infeccioso e no plasma, avaliado pela mensuração de nitrito + nitrato. A sepse também induziu aumento precoce da concentração de LXA4 no foco infeccioso e da expressão do seu receptor FPR2/ALX nos pulmões. O tratamento com o antagonista do receptor FPR2/ALX, BOC-1, no início da sepse aumentou a migração de leucócitos para o foco, reduziu o processo infeccioso local e a sua disseminação, e aumentou a sobrevida dos animais. Por outro lado, nos animais tratados com a LXA4 ou com o seu análogo BML-111 no início da sepse, houve redução da migração de células para o foco e agravamento do processo infeccioso. Em momentos mais avançados da sepse, o tratamento dos camundongos com BOC-1 não teve efeito na sobrevida. Entretanto, o tratamento tardio com a LXA4 e o BML-111 aumentou a sobrevida por reduzir a resposta inflamatória excessiva. Esse estudo mostra que a infecção pulmonar induzida pela K. pneumoniae é um modelo animal de sepse clinicamente relevante que induz uma resposta inflamatória sistêmica e provoca alterações cardiovasculares que persistem por pelo menos 48 h. Nossos achados mostram que os níveis de LXA4 e do seu receptor FPR2/ALX estavam aumentados no início da sepse contribuindo para a resposta inflamatória desordenada que ocorre nessa patologia. Além disso, nossos dados mostram que a LXA4 tem um papel duplo na sepse, e seu efeito benéfico ou maléfico é tempo-dependente. Portanto, uma interferência apropriada na via LXA4-FPR2/ALX pode constituir uma nova estratégia terapêutica no auxílio do tratamento da sepse.
Abstract: Pneumonia is one of the major causes of sepsis, which, in turn, is the main cause of death in intensive care units, in spite of recent medical advances. The study of sepsis and new therapeutic alternatives remains challenging due to the complexity of this syndrome, whose main component is a dysregulated inflammatory response. Lipoxin A4 (LXA4) is an endogenous lipid mediator with potent anti-inflammatory e proresolution actions but its role in infectious processes like sepsis is not well understood. Thus, the aim of the present work was to provide a better comprehension of the role of LXA4 and its receptor FPR2/ALX in the inflammatory dysregulation that occurs in pneumonia-induced sepsis model. Pneumosepsis was induced in Swiss male mice by Klebsiella pneumoniae intratracheal inoculation. Inflammatory and cardiovascular parameters were evaluated 6, 24 and 48 h after the insult. The results show that severity of infection and the mortality correlated with the amount of bacteria. Septic animals presented pathological changes in lungs, increase in cell number in the bronchoalveolar lavage, leukopenia, increase in TNF-a and IL-1ß levels, hypotension and hyporesponsiveness to vasoconstrictors, the two latter characteristics of severe sepsis and septic shock. Significant numbers of bacteria in spleen and heart homogenates indicated infection spreading. Interestingly, NOS-2 expression appeared late after bacteria inoculation, whereas levels of NOS-1 and NOS-3 were unchanged. The high NOS-2 expression coincided with an exacerbated NO production in the infection focus and in plasma, as judging by nitrate + nitrite levels. Sepsis also induced an early increase in LXA4 levels and an augment in its receptor FPR2/ALX expression in lungs. Treatment in early sepsis with the antagonist of FPR2/ALX, BOC-1, increased leukocyte migration to the focus, reduced bacterial load and dissemination and improved survival. On the other hand, animals treated with LXA4 itself or the analog BML-111 in early sepsis exhibited a decrease in cell migration to the focus and an infection worsening. In late sepsis, treatment of mice with BOC-1 had no effect, but LXA4 and BML-111improved the survival rate by reducing the excessive inflammatory response. This study shows that K. pneumoniae-induced lung infection is a clinically relevant animal model of sepsis inducing a systemic inflammatory response and cardiovascular alterations which endures at least until 48 h. Our findings demonstrate that LXA4 and its receptor FPR2/ALX levels were increased in the early phase of sepsis, contributing to the characteristic inflammatory dysregulation that occurs in this pathology. In addition, our data show that LXA4 has a dual role in sepsis and that its beneficial or harmful effects are critically dependent on the time. Therefore, a proper interference with LXA4 system may open a new therapeutic avenue to treat sepsis.
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Martini, Alessandra Cadete. "Lipoxina A4 na dor neuropática após a lesão medular: modulação da neuroinflamação e ativação microglial." reponame:Repositório Institucional da UFSC, 2015. https://repositorio.ufsc.br/xmlui/handle/123456789/135397.
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Tese (doutorado) - Universidade Federal de Santa Catarina, Centro de Ciências Biológicas, Programa de Pós-Graduação em Farmacologia, Florianópolis, 2015.Made available in DSpace on 2015-10-06T04:07:47Z (GMT). No. of bitstreams: 1 334506.pdf: 6602954 bytes, checksum: 2edbe2671a45d091e8252ddc6bd67d9e (MD5) Previous issue date: 2015
A dor crônica está presente na maioria dos pacientes após a lesão medular traumática (LMT). As respostas inflamatórias após a lesão medular estão relacionadas com o desenvolvimento da dor neuropática através da ativação de um vasto número de mediadores e vias de sinalização. A lipoxina A4 (LXA4), um eicosanoide com propriedades anti-inflamatórias e pró-resolução, exerce ações neuroprotetoras e anti-hiperalgésicas. Entretanto, seu papel na dor neuropática induzida pela lesão medular ainda não foi elucidado. Sob completa anestesia, ratos Wistar e camundongos CD1 machos receberam uma hemissecção medular na porção esquerda do segmento T10. Em 4 e 24 horas após a lesão, os animais foram tratados por via intratecal com LXA4 (150 ou 300 pmol) ou veículo. Em outro protocolo, foi realizado o silenciamento gênico do receptor de lipoxina A4, ALX/FPR2, através do tratamento por via intratecal com ALX/FPR2 RNAsi. A sensibilidade mecânica das patas posteriores foi avaliada após a lesão medular através da frequência de resposta ao filamento de von Frey de 15 g em ratos e por uma sequência de filamentos (método up-down) em camundongos. No 7° dia após a cirurgia, a medula espinhal foi coletada e processada para análise do teor endógeno de LXA4 e também dos níveis de expressão do receptor ALX/FPR2, marcadores gliais e citocinas, por RT-PCR. Culturas de microglia também foram preparadas a partir do córtex cerebral de camundongos para avaliação dos efeitos diretos da LXA4 na expressão de citocinas e ativação de proteínas quinases (MAPK) nestas células. Todos os procedimentos foram aprovados pelos comitês de ética locais. Os animais falso-operados apresentaram sensibilidade mecânica normal após a cirurgia. Houve aumento da resposta ao estímulo de von Frey em ambas as patas posteriores de ratos a partir do dia 7 e até o dia 28 após a cirurgia. Os camundongos apresentaram aumento de sensibilidade da pata posterior ipsilateral a partir do 14° dia e da pata contralateral a partir do 7° dia, a qual durou pelos 35 dias de observação. Houve aumento da expressão do RNAm do receptor ALX/FPR2 no 7° dia após a lesão em ambas as espécies. O tratamento intratecal com LXA4 reduziu a hiperalgesia mecânica, em comparação ao grupo tratado com veículo, em ratos e camundongos, mas o silenciamento gênico do receptor em camundongos bloqueou este efeito. A LXA4 também reduziu os níveis das citocinas pró-inflamatórias IL-1ß, IL-6 e TNF-a, e aumentou o nível da citocina anti-inflamatória IL-10, na medula espinhal de ratos. Finalmente, a LXA4 reduziu a ativação de p38 e a liberação de TNF-a induzidas por IFN-? em culturas de microglia. Em conjunto, nossos resultados sugerem que a LXA4 pode reduzir efetivamente a dor neuropática após a lesão medular em roedores, pela inibição da neuroinflamação e das respostas da microglia na medula espinhal. Assim, a LXA4 e seus análogos poderiam ser utilizados para prevenção da dor neuropática e da neuroinflamação induzidas pela lesão medular.
Abstract : It is well known that after traumatic spinal cord injury (SCI) majority of patients develop chronic pain syndromes. Spinal inflammatory responses to SCI have been implicated in the onset of neuropathic pain via activation of a broad spectrum of factors and signaling pathways. Lipoxin A4 (LXA4), an eicosanoid endowed with anti-inflammatory and pro-resolution properties, exerts neuroprotective and antihyperalgesic effects. However, its role in SCI-induced neuropathic pain still remains to be elucidated. Spinal cord hemisection at the left side of T10 was carried out in anesthetized adult male Wistar rats and CD1 mice. At 4 and 24 h after SCI, the animals received two intrathecal LXA4 (150 pmol or 300 pmol) or vehicle injections. In a different protocol, animals also received an intrathecal treatment of ALX/FPR2 siRNA for receptor gene silencing. Mechanical sensitivity of hind paws was evaluated after SCI using a 15g von Frey hair in rats or with a series of von Frey hairs in mice (up-down method). On the 7th day after surgery the spinal cord was collected and processed to evaluate the levels of endogenous LXA4 as well as the transcriptional expression level by RT-PCR of the ALX/FPR2 receptor, cytokines and glial markers. Microglia cultures were also prepared from mice cerebral cortexes to assess the direct effects of LXA4 on microglial cytokine expression and MAPK activation. The local ethics committees approved all procedures. Shamoperated animals showed normal mechanical responsiveness after the surgery. The mechanical responsiveness to von Frey hair was increased on both rat hind paws from day 7 until day 28 after SCI. Mice started presenting increased sensitivity on the ipsilateral paw on day 14 and in the contralateral paw on day 7, until the 35th days of observation. The ALX/FPR2 receptor mRNA was significantly increased in both species on the 7th day after SCI. Intrathecal treatment of LXA4 reduced SCIinduced mechanical hypersensitivity when compared to vehicle control group in both rats and mice, but the gene silencing with the respective siRNA in mice for the receptor blocked this effect. The LXA4 treatment also reduced the levels of the pro-inflammatory cytokines IL-1ß, IL-6 and TNF-a and increased the levels of the anti-inflammatory cytokine IL-10,on rat spinal cord. Finally, LXA4 reduced the IFN-?-induced p38 activation and TNF-a release in microglia cultures. Taken together, our results suggest that LXA4 can effectively reduce neuropathic pain in rodents after SCI, by inhibiting SCI-induced neuroinflammation in the spinal cord and microglial responses. Thus, LXA4 and its analogs may be used to prevent SCI-induced neuropathic pain and neuroinflammation.
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Leo, Luciana Magalhães. "Papel da Lipoxina A4 na fisiologia do sistema nervoso central e no dano cognitivo associado à neuroinflamação." reponame:Repositório Institucional da FIOCRUZ, 2015. https://www.arca.fiocruz.br/handle/icict/12858.
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Previous issue date: 2016-02-23O papel da lipoxina A4 (LXA4) no sistema imunológico é bem estudado, mas o papel dessa molécula na fisiologia do sistema nervoso central (SNC) só foi abordado recentemente. Como um modulador alostérico positivo, a LXA4 produz efeitos canabimiméticos e pode, dessa forma, estar envolvida em vários aspectos de funções fisiológicas reguladas pelo sistema endocanabinóide (eCB). Nós investigamos essa hipótese analisando o comportamento de camundongos knockout (5-LO-/-) para a enzima 5-lipoxigenase (5-LO), que participa da síntese de LXA4. Ansiedade, consumo de água e alimento, locomoção, nocicepção e memórias aversivas são comportamentos reconhecidos como sob controle do sistema eCB e foram avaliados neste estudo. Nenhuma alteração foi observada no comportamento de 5-LO-/- em relação ao consumo de água e alimento e locomoção no teste de campo aberto. No entanto, o tratamento com LXA4 produziu efeito ansiolítico no labirinto em cruz elevada. Além disso, inibição farmacológica da 5- LO demonstrou um efeito ansiogênico em animais idosos, mas não em adultos jovens, indicando que a LXA4 endógena exerce um efeito regulatório sobre ansiedade de forma idade-dependente. Os animais 5-LO-/- apresentaram um aumento na sensibilidade e redução na tolerância à dor no teste de sensibilidade ao choque. Ainda, uma disfunção em memória de curto prazo e extinção de memória no teste de esquiva inibitória foi observada nos animais 5-LO-/-, indicando que a LXA4 pode agir na facilitação do aprendizado. Esse dado é de grande importância para o possível uso da LXA4 como tratamento do dano cognitivo decorrente de neuroinflamação O estudo da sepse nos revela que um estímulo inflamatório pode gerar produção exacerbada de moléculas pró-inflamatórias no SNC, o que causa neuroinflamação e disfunção cognitiva. A LXA4 é uma boa candidata como alvo de terapia para o dano cognitivo decorrente de neuroinflamação, uma vez que tem potencial anti-inflamatório e neuroprotetor por ação em receptores ALX e CB1, respectivamente. Neste estudo foi possível observar queda na produção de citocinas pró-inflamatórias no plasma e no cérebro de camundongos com inflamação sistêmica induzida por lipopolissacarídeo (LPS) mediante tratamento com LXA4. Além disso, o dano cognitivo observado sobre consolidação de memória neste modelo de sepse foi prevenido após tratamento com LXA4. Os dados apresentados neste estudo apontam funções do SNC sujeitas a modulação pela disponibilidade de LXA4 endógena e um efeito benéfico do tratamento da LXA4 no resgate de dano cognitivo decorrente de neuroinflamação. Apresentamos evidências que contribuem para o esclarecimento do papel fisiológico da LXA4 no SNC e para o seu potencial no tratamento de patologias inflamatórias que atingem o encéfalo
The role of lipoxin A 4 (LXA 4 ) in the immune system is well studied, however the part this molecule play s in central nervous system (CNS) physiology has only recently been addressed. LXA 4 , as a CB1 allosteric enhancer, has a cannabimimetic effect and may therefore be involved in various aspects of endocannabinoid system (eCB) physiological functions. We investigated this reasoning by analyzing the behavior of 5 - lipoxygenase ( 5 - LO ) knockout mice (5 - LO - / - ) . A nxiety - like behavior, a ppetitive behavior, locomotion, nociception and learning and memory are all known to be under control of the eCB system and were assessed in this study. No alteration was observed in the behavior of 5 - LO knockout mi ce regarding appetitive behavior, measured by food and water intake, or locomotion in the open field test. However, treatment with LXA 4 produced an anxiolytic - like effect on the elevated plus maze. Further, pharmacological inhibition of 5 - LO showed a n anxi ogenic - like effect in aged, but not adult mice, indicating that endogenous LXA 4 has an age - dependent effect on the modulation of anxiety - like behavior. 5 - LO - / - mice presented an increase in pain sensitivity and a decrease in pain tolerance in the foot shoc k sensitivity test. Interestingly, the animals also presented impairment in short - term memory and extinction learning in the step - down inhibitory avoidance task, pointing out that LXA 4 may act in the facilitation of fear learning. These data are of great i mportance to the possible use of LXA 4 as treatment to neuroinflammation induced cognitive impairment. The study of sepsis reveals that an inflammatory stimulus can induce the exacerbated production of pro - inflammatory cytokines in the CNS, which causes neu roinflammation and cognitive impairment. LXA 4 is a good candidate as target in the treatment of neuroinflammation induced cognitive impairment, since it has anti - inflammatory and neuroprotection potential due to its action on ALX and CB1 receptors, respect ively. In this study, we observed a decrease in the production of pro - inflammatory cytokines in plasma and brain of mice with induced systemic inflammation by lipopolysaccharide (LPS) injection due to treatment with LXA 4 . Moreover, the memory consolidation impairment observed in this sepsis animal model was prevented following LXA 4 treatment. The data presented in this study point out CNS functions subjected to modulation by endogenous LXA 4 availability and a beneficial effect of LXA 4 tr eatment on neuroinflammation induced cognitive impairment. We present evidence that contributes to the understanding of the physiological role of LXA4 in the CNS and its potential in the treatment of inflammatory pathologies that affect the brain
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Reis, Mouzarllem Barros dos. "Avaliação da influência da lipoxina A4 encapsulada em micropartículas de PLGA na cicatrização de úlceras cutâneas em ratos." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/17/17147/tde-05012017-095359/.
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Lipoxina A4 (LXA4) é um eicosanoide derivado do metabolismo do ácido araquidônico pelas lipoxigenases (5, 12 e 15-LO), tendo propriedades antiinflamatórias e pró-resolução. A estratégia de uso de LXA4 encapsulada em micropartículas de PLGA como fármaco tem fundamento nas propriedades que tais polímeros têm de preservar as atividades biológicas de moléculas diversas, como dos lipídeos, e promover liberação prolongada e sustentada das mesmas. No presente estudo, tivemos como hipótese de trabalho que a encapsulação de LXA4 em micropartículas de PLGA (LXA4-MS) preserva suas atividades biológicas, e mais eficientemente, acelera o fechamento de úlceras induzidas na pele de ratos. Para tanto, um modelo de úlceras cutâneas na região dorsal de ratos foi utilizado. As LXA4-MS foram fixadas em pele com adesivo biológico de fibrina, e seus efeitos comparados com aqueles induzidos por micropartículas vazias (Un-MS), LXA4 solúvel ou veículo (PBS). Nossos resultados mostraram que LXA4-MS aceleram a cicatrização da ferida, pois no 7º dia após a lesão, reduziu em 80% o diâmetro da úlcera inicial, enquanto no mesmo período, nas úlceras tratadas com LXA4 solúvel, Un-MS ou veículo ocorreu diminuição de somente 60%, 45% e 39%, respectivamente. O aumento do índice de cicatrização induzido pelo tratamento das úlceras com LXA4-MS foi acompanhado pela diminuição das citocinas pró-inflamatórias IL- 1?, TNF-?, e aumento de TGF- ?, uma citocina antiinflamatória indutora da deposição de colágeno. Além disso, nas úlceras tratadas com LXA4-MS o infiltrado inflamatório foi reduzido no tecido de cicatrização, como demonstrado pela diminuição de infiltrado celular, de MPO e de mRNA da metaloproteinase MMP8. Por outro lado, LXA4-MS induziu aumento da deposição de colágeno e do número de vasos sanguíneos, de NAG e de IL-4, quando comparado com os demais tratamentos. Quando as úlceras foram tratadas concomitantemente com LXA4-MS e o antagonista do receptor de LXA4 (ciclosporina H), observamos reversão de cerca de 50% no índice de cicatrização promovido pelo mediador encapsulado, sugerindo que os efeitos tópicos do tratamento com LXA4 são devidos à sua interação com seu receptor específico. Nossos resultados sugerem que novas formulações farmacêuticas para tratamento de úlceras cutâneas poderão ser obtidas com LXA4-MS.Lipoxin A4 (LXA4) is an eicosanoid derived from the metabolism of arachidonic acid by lipoxygenases (5, 12, and 15-LO), having anti-inflammatory and pro-resolution properties. The strategy of using LXA4 encapsulated in PLGA microparticles as drug is due to some properties that such polymers have to preserve the biological activity of several molecules such as lipids, and promote a prolonged and sustained release of these molecules. In the present study, we hypothesized that the encapsulation of LXA4 in PLGA microparticles (LXA4-MS) preserves its biological activities, and more efficiently accelerates the closing of ulcers induced in the skin of rats. Thus, a model for cutaneous ulcers in the dorsal region of rats was used. The LXA4-MS were fixed in skin using biological adhesive of fibrin, and their effects compared to those induced by empty microparticles (Un-MS), soluble LXA4 or vehicleOur results showed that LXA4-MS accelerate wound healing, once on day 7 after injury, reduced by 80% the diameter of the initial ulcer, while at the same time, the ulcers treated with soluble LXA4, Un-MS or vehicle was decreased of only 60%, 45% and 39%, respectively. The increased healing rate of ulcers induced by treatment with LXA4-MS was accompanied by the decrease of pro-inflammatory cytokines IL-1?, TNF-?, and a TGF-? increasing, an anti-inflammatory cytokine-inducing collagen deposition. In addition, the inflammatory infiltrate was reduced in scar tissue as demonstrated by the decrease of neutrophils, MPO and MMP8 metalloproteinase mRNA. Moreover, LXA4-MS induced increase in collagen deposition and the number of blood vessels when compared with the other controls. When the ulcers were treated concomitantly with LXA4-MS and the antagonist LXA4 receptor (ALX), cyclosporine H, we observed the reversal of about 50% in healing rates promoted by the encapsulated agent, suggesting that topical treatment effects of LXA4 are due to interaction with its own receptor. Our results suggest that new pharmaceutical formulations for the treatment of skin ulcers can be obtained with LXA4-MS.
Books on the topic "Lipoxine A4"
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Duffy, Colm. Heteroaromatic Lipoxin A4 Analogues. Berlin, Heidelberg: Springer Berlin Heidelberg, 2012. http://dx.doi.org/10.1007/978-3-642-24632-6.
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service), SpringerLink (Online, ed. Heteroaromatic Lipoxin A4 Analogues: Synthesis and Biological Evaluation. Berlin, Heidelberg: Springer Berlin Heidelberg, 2012.
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Duffy, Colm. Heteroaromatic Lipoxin A4 Analogues: Synthesis and Biological Evaluation. Springer, 2014.
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Heteroaromatic Lipoxin A4 Analogues Synthesis And Biological Evaluation. Springer, 2012.
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Duffy, Colm. Heteroaromatic Lipoxin A4 Analogues: Synthesis and Biological Evaluation. Springer, 2012.
Find full textBook chapters on the topic "Lipoxine A4"
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Wilson, John Fawcett. "Lipoxin A4." In The Immunoassay Kit Directory, 1798. Dordrecht: Springer Netherlands, 1995. http://dx.doi.org/10.1007/978-94-011-0679-5_84.
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Duffy, Colm. "Introduction." In Heteroaromatic Lipoxin A4 Analogues, 1–9. Berlin, Heidelberg: Springer Berlin Heidelberg, 2012. http://dx.doi.org/10.1007/978-3-642-24632-6_1.
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Duffy, Colm. "Recent Advances in the Chemistry and Biology of Stable Synthetic Lipoxin Analogues." In Heteroaromatic Lipoxin A4 Analogues, 11–39. Berlin, Heidelberg: Springer Berlin Heidelberg, 2012. http://dx.doi.org/10.1007/978-3-642-24632-6_2.
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Duffy, Colm. "Synthesis of Heck Coupling Partner for the Preparation of Heteroaromatic Lipoxin A4 Analogues." In Heteroaromatic Lipoxin A4 Analogues, 41–53. Berlin, Heidelberg: Springer Berlin Heidelberg, 2012. http://dx.doi.org/10.1007/978-3-642-24632-6_3.
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Duffy, Colm. "Synthesis and Biological Evaluation of Pyridine-Containing Lipoxin A4 Analogues." In Heteroaromatic Lipoxin A4 Analogues, 55–82. Berlin, Heidelberg: Springer Berlin Heidelberg, 2012. http://dx.doi.org/10.1007/978-3-642-24632-6_4.
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Duffy, Colm. "Thiophene-Containing Lipoxin A4 Analogues: Synthesis and Their Effect on the Production of Key Cytokines." In Heteroaromatic Lipoxin A4 Analogues, 83–108. Berlin, Heidelberg: Springer Berlin Heidelberg, 2012. http://dx.doi.org/10.1007/978-3-642-24632-6_5.
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Duffy, Colm. "Towards the Synthesis of Various Heteroaromatic Lipoxin A4 Analogues." In Heteroaromatic Lipoxin A4 Analogues, 109–27. Berlin, Heidelberg: Springer Berlin Heidelberg, 2012. http://dx.doi.org/10.1007/978-3-642-24632-6_6.
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Dahlén, Sven-Erik, Lilian Franzén, Johan Raud, Eva Wikström, Thure Björck, Hisao Matsuda, Pär Westlund, et al. "Actions of Lipoxin A4 and Related Compounds in Smooth Muscle Preparations and on the Microcirculation in Vivo." In Lipoxins, 107–30. Boston, MA: Springer US, 1988. http://dx.doi.org/10.1007/978-1-4757-0937-7_9.
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Serhan, Charles N., Tomoko Takano, and Jane F. Maddox. "Aspirin-Triggered 15-Epi-Lipoxin A4 and Stable Analogs of Lipoxin A4 are Potent Inhibitors of Acute Inflammation." In Advances in Experimental Medicine and Biology, 133–49. Boston, MA: Springer US, 1999. http://dx.doi.org/10.1007/978-1-4615-4861-4_13.
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Funk, Colin D., Xin-Sheng Chen, and Garret A. Fitzgerald. "Lipoxygenase, Cyclooxygenase and Leukotriene A4 Hydrolase: Quantitative Polymerase Chain Reaction and Expression Studies." In Prostaglandins, Leukotrienes, Lipoxins, and PAF, 97–105. Boston, MA: Springer US, 1991. http://dx.doi.org/10.1007/978-1-4899-0727-1_11.
Full textConference papers on the topic "Lipoxine A4"
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Al-Alawi, Mazen, Valia Verriere, Olive McCabe, Richard W. Costello, Valerie Urbach, and Brian J. Harvey. "Effect Of Lipoxin A4 In Modifying The Bronchial Airway Surface Liquid Layer." In American Thoracic Society 2010 International Conference, May 14-19, 2010 • New Orleans. American Thoracic Society, 2010. http://dx.doi.org/10.1164/ajrccm-conference.2010.181.1_meetingabstracts.a1392.
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Uddin, Mohib, Olaf Eickmeier, and Bruce D. Levy. "Lipoxin A4 Regulates Epidermal Growth Factor Signaling In Human Airway Epithelial Cells." In American Thoracic Society 2010 International Conference, May 14-19, 2010 • New Orleans. American Thoracic Society, 2010. http://dx.doi.org/10.1164/ajrccm-conference.2010.181.1_meetingabstracts.a1063.
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