InChI=1S/C20H32O5/c1-2-3-8-12-17(21)13-9-6-4-5-7-10-14-18(22)19(23)15-11-16-20(24)25/h4-7,9-10,13-14,17-19,21-23H,2-3,8,11-12,15-16H2,1H3,(H,24,25)/b6-4-,7-5+,13-9+,14-10+/t17-,18+,19-/m0/s1 |
IXAQOQZEOGMIQS-SSQFXEBMSA-N |
CCCCC[C@H](O)\C=C\C=C/C=C/C=C/[C@@H](O)[C@@H](O)CCCC(O)=O |
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Homo sapiens
(NCBI:txid9606)
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See:
DOI
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Bronsted acid
A molecular entity capable of donating a hydron to an acceptor (Bronsted base).
(via oxoacid )
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human metabolite
Any mammalian metabolite produced during a metabolic reaction in humans (Homo sapiens).
metabolite
Any intermediate or product resulting from metabolism. The term 'metabolite' subsumes the classes commonly known as primary and secondary metabolites.
specialised pro-resolving mediator
A class of cell signaling molecules enzymatically derived from n-3 long chain polyunsaturated fatty acids that have important roles in orchestrating the resolution of tissue inflammation.
(via lipoxin )
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specialised pro-resolving mediator
A class of cell signaling molecules enzymatically derived from n-3 long chain polyunsaturated fatty acids that have important roles in orchestrating the resolution of tissue inflammation.
(via lipoxin )
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View more via ChEBI Ontology
(5S,6R,7E,9E,11Z,13E,15S)-5,6,15-trihydroxyicosa-7,9,11,13-tetraenoic acid
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(5S,6R,15S)-trihydroxy-7,9,13-trans-11-cis-eicosatetraenoic acid
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ChEBI
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(5S,6R,7E,9E,11Z,13E,15S)-5,6,15-trihydroxy-7,9,11,13-eicosatetraenoic acid
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ChEBI
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(5S,6R,7E,9E,11Z,13E,15S)-5,6,15-trihydroxyeicosa-7,9,11,13-tetraenoic acid
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ChEBI
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(7E,9E,11Z,13E)-(5S,6R,15S)-5,6,15-Trihydroxyicosa-7,9,11,13-tetraenoic acid
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KEGG COMPOUND
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5(S),6(R),15(S)-trihydroxyeicosa-7E,9E,11Z,13E-tetraenoic acid
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ChEBI
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5S,6R,15S-trihydroxy-7,9,13-trans-11-cis-eicosatetraenoic acid
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ChEBI
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5S,6R,15S-Trihydroxy-7E,9E,11Z,13E-eicosatetraenoic acid
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KEGG COMPOUND
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5S,6R-LipoxinA4
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LIPID MAPS
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6R-LXA4
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ChEBI
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Lipoxin A4
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KEGG COMPOUND
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lipoxin A4
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ChEBI
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LXA4
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KEGG COMPOUND
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LXA4
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ChEBI
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4698639
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Reaxys Registry Number
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Reaxys
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Maldonado-Pérez D, Golightly E, Denison FC, Jabbour HN, Norman JE (2011) A role for lipoxin A4 as anti-inflammatory and proresolution mediator in human parturition. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 25, 569-575 [PubMed:20959513] [show Abstract] The purpose of this study was to investigate the role of lipoxin A(4), an anti-inflammatory and proresolution modulator, during human parturition. We measured serum levels of lipoxin A(4) and myometrial protein release using ELISA, quantified lipoxin receptor (FPR2/ALX) mRNA expression using qRT-PCR, and localized protein expression using immunohistochemstry in myometrial biopsies from pregnant women. In addition, we compared the effects of lipoxin A(4) (100 nM) with vehicle on basal and LPS-stimulated expression of proinflammatory cytokines from samples of myometrium from pregnant women. Mean ± SE circulating level of lipoxin A(4) was 5.89 ± 0.63 nM at 24-wk gestation, with a further modest increase during pregnancy (P<0.05), but no differences in gestation matched women before and after labor (P>0.05). Levels of lipoxin A(4) in nonpregnant women were 0.48 ± 0.04 nM, significantly lower than in pregnant women (P<0.001). FPR2/ALX localized to myocytes and neutrophils, with a 9-fold increase in mRNA expression in labor (P<0.001). Lipoxin A(4) significantly reduced LPS-induced but not basal expression of the proinflammatory cytokines IL-6 and IL-8 in cultured myometrium (P<0.05), compared to vehicle-treated controls. We demonstrate for the first time a potential role for lipoxin A(4) and its receptor in the resolution of the inflammatory events of both physiological and pathological labor. | Börgeson E, Lönn J, Bergström I, Brodin VP, Ramström S, Nayeri F, Särndahl E, Bengtsson T (2011) Lipoxin A₄ inhibits porphyromonas gingivalis-induced aggregation and reactive oxygen species production by modulating neutrophil-platelet interaction and CD11b expression. Infection and immunity 79, 1489-1497 [PubMed:21263017] [show Abstract] Porphyromonas gingivalis is an etiological agent that is strongly associated with periodontal disease, and it correlates with numerous inflammatory disorders, such as cardiovascular disease. Circulating bacteria may contribute to atherogenesis by promoting CD11b/CD18-mediated interactions between neutrophils and platelets, causing reactive oxygen species (ROS) production and aggregation. Lipoxin A₄ (LXA₄) is an endogenous anti-inflammatory and proresolving mediator that is protective of inflammatory disorders. The aim of this study was to investigate the effect of LXA₄ on the P. gingivalis-induced activation of neutrophils and platelets and the possible involvement of Rho GTPases and CD11b/CD18 integrins. Platelet/leukocyte aggregation and ROS production was examined by lumiaggregometry and fluorescence microscopy. Integrin activity was studied by flow cytometry, detecting the surface expression of CD11b/CD18 as well as the exposure of the high-affinity integrin epitope, whereas the activation of Rac2/Cdc42 was examined using a glutathione S-transferase pulldown assay. The study shows that P. gingivalis activates Rac2 and Cdc42 and upregulates CD11b/CD18 and its high-affinity epitope on neutrophils, and that these effects are diminished by LXA₄. Furthermore, we found that LXA₄ significantly inhibits P. gingivalis-induced aggregation and ROS generation in whole blood. However, in platelet-depleted blood and in isolated neutrophils and platelets, LXA₄ was unable to inhibit either aggregation or ROS production, respectively. In conclusion, this study suggests that LXA₄ antagonizes P. gingivalis-induced cell activation in a manner that is dependent on leukocyte-platelet interaction, likely via the inhibition of Rho GTPase signaling and the downregulation of CD11b/CD18. These findings may contribute to new strategies in the prevention and treatment of periodontitis-induced inflammatory disorders, such as atherosclerosis. | Das UN (2011) Lipoxin A4 may function as an endogenous anti-arrhythmic molecule. Medical hypotheses 76, 14-16 [PubMed:20833483] [show Abstract] Cardiac arrhythmias cause significant morbidity and mortality in patients with coronary heart disease, hypertension, and congestive cardiac failure and in the elderly. Inflammation, oxidative injury, altered myocyte metabolism, extracellular matrix remodeling and fibrosis initiate and perpetuate cardiac arrhythmias, especially atrial fibrillation. Enhanced myeloperoxidase (MPO) activity by infiltrating activated leukocytes could bind to myocardial cells and cause fibrosis resulting in the initiation and progression of arrhythmias. Supplementation of eicosapentaenoic and docosahexaenoic acids (EPA and DHA, respectively) suppresses arrhythmias. EPA and DHA form precursors to anti-inflammatory lipid molecules: lipoxins, resolvins, protectins and maresins that are known to suppress inflammation, have anti-fibrotic actions and inhibit MPO activity. Hence, it is likely that leukocyte and/or myocardial deficiency of EPA and DHA and consequent reduced formation of lipoxins, resolvins, protectins and maresins enhance inflammation and MPO activity that leads to myocardial damage and fibrosis and initiation and progression of cardiac arrhythmias. Based on these evidences, I propose that lipoxins, resolvins and protectins function as endogenous anti-arrhythmic molecules and their stable synthetic analogs could be useful in the management of cardiac arrhythmias. | Zhou M, Chen B, Sun H, Deng Z, Andersson R, Zhang Q (2011) The protective effects of Lipoxin A4 during the early phase of severe acute pancreatitis in rats. Scandinavian journal of gastroenterology 46, 211-219 [PubMed:20950211] [show Abstract]
ObjectiveOur aim was to investigate the protective effects of a Lipoxin A(4) analogue (LXA4) in the early phase of acute pancreatitis in rats.Materials and methodsSevere acute pancreatitis (SAP) was induced by injection of 5% sodium taurocholate into the pancreatic duct. Rats with SAP were treated with LXA4 (0.1 mg/kg), 10 min after the 5% sodium taurocholate injection, after which LXA4 was administrated every 8 hours, three times (LXA4 group). The sham group was only given the vehicle after operation. Plasma amylase activity, serum levels of interleukin-1 (IL-1), IL-6, and tumor necrosis factor-α (TNF-α) were measured at 4, 12, and 24 h after induction of SAP. The pancreatic index and histopathologic observations were evaluated and the expression of intercellular adhesion molecule-1 (ICAM-1) and NF-κB p65 in the pancreas, and the expression of ICAM-1 in the lungs were detected by immunohistochemistry.ResultsLXA4 treated rats had lower serum levels of TNF-α, IL-1, and IL-6 at all time points measured (p < 0.05), but significantly differed in plasma amylase activity only at 24 h as compared with the SAP group. The pancreatic index and the scores of pancreatitic histopathologic evaluations were lower in the LXA4 group as compared to the SAP group. Immunohistochemistry showed that LXA4 attenuated the expression of ICAM-1 and NF-κB p65 in the pancreas, as well as the expression of ICAM-1 in the lungs in animals with pancreatitis (p < 0.05).ConclusionsWe demonstrate that LXA4 has protective effects in experimental SAP, which may be achieved by inhibiting the NF-κB signalling pathway, thereby reducing the production of proinflammatory cytokines. | Chan MM, Moore AR (2010) Resolution of inflammation in murine autoimmune arthritis is disrupted by cyclooxygenase-2 inhibition and restored by prostaglandin E2-mediated lipoxin A4 production. Journal of immunology (Baltimore, Md. : 1950) 184, 6418-6426 [PubMed:20435922] [show Abstract] Acute inflammation follows defined phases of induction, inflammation and resolution, and resolution occurs by an active process that requires cyclooxygenase-2 (COX-2) activity. This study aims to address whether this paradigm extends to recognized model of chronic inflammation. We demonstrated that murine collagen-induced arthritis follows a similar sequential course. Interestingly, COX-2 and its metabolite, the presumably proinflammatory PGE(2), are present in the joints during resolution, and blocking COX-2 activity and PGE(2) production within this period perpetuated, instead of attenuated, inflammation. Repletion with PGE(2) analogs restored homeostasis, and this function is mediated by the proresolving lipoxygenase metabolite, lipoxin A(4), a potent stop signal. Thus, the study provided in vivo evidence for a natural, endogenous link between the cyclooxygenase-lipoxygenase pathways and showed that PGE(2) serves as a feedback inhibitor essential for limiting chronic inflammation in autoimmune arthritis. These findings may explain the enigma regarding why COX-2 inhibitors are palliative rather than curative in humans, because blocking resolution may mitigate the benefit of preventing induction. | Das UN (2010) Is lipoxins A4 a better alternative to anti-TNF-alpha antibody to prevent and treat diabetic macular edema and retinopathy? Medical science monitor : international medical journal of experimental and clinical research 16, LE13-4 [PubMed:20802423] | Papayianni A, Serhan CN, Brady HR (1996) Lipoxin A4 and B4 inhibit leukotriene-stimulated interactions of human neutrophils and endothelial cells. Journal of immunology (Baltimore, Md. : 1950) 156, 2264-2272 [PubMed:8690917] [show Abstract] Lipoxins are bioactive eicosanoids that are generated within the vascular lumen by leukocytes and transcellular biosynthetic routes during multicellular responses. Polymorphomuclear neutrophils (PMN) and endothelial cells express high affinity receptors for lipoxins, engagement of which invokes profiles of signaling events that differ from other lipid mediators. In this work, we report that lipoxins are potent inhibitors of PMN-endothelial cell interactions triggered by leukotrienes via dual-pronged actions with PMN and endothelial cells. Both lipoxin A4(LXA4) and B4(LXB4) blocked PMN migration stimulated by leukotriene B4 (LTB4), a well established agonist for PMN recruitment, a transmigration assay in vitro. Lipoxins were almost as effective in this regard as the pharmacologic LTB4 receptor antagonist, ONO 4057, and the blocking anti-CD18 mAb, R15.7. LXA4 and LXB4 blunted PMN transmigration, in part by inhibiting beta 2 integrin-dependent PMN adhesion. These modulatory actions of lipoxins were evident at subnanomolar concentrations, rapid in onset, and attenuated by prior exposure of PMN to a tyrosine kinase inhibitor, genistein. The peptidoleukotrienes, leukotriene C4 (LTC4) and leukotriene D4 (LTD4) also provoked PMN-endothelial cell adhesion, but via a different mechanism than LTB4. Both LTC4 and LTD4 enhanced endothelial adhesiveness for PMN, in part, by stimulating mobilization of P-selectin from intracellular Weibel-Palade bodies. LXA4 and LXB4, but not other lipoxygenase products, blocked P-selectin mobilization induced by peptidoleukotrienes and attenuated P-selectin-mediated PMN-endothelial cell adhesion. These results indicate that lipoxins attenuate PMN-endothelial cell interactions supported by selectins and beta 2 integrins in vitro, and are potential endogenous lipid-derived modulators of PMN trafficking in host defense, inflammation, and other vascular events. |
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