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• W1818367061 abstract "BACKGROUND AND PURPOSE Lipoxin A 4 (LXA 4 ) is a lipid mediator involved in the resolution of inflammation. Increased levels of LXA 4 in synovial fluid and enhanced expression of the formyl peptide receptor 2/lipoxin A 4 receptor (FPR2/ALX) in the synovial tissues of rheumatoid arthritis patients have been reported. Endothelins (ETs) play a pivotal pro‐inflammatory role in acute articular inflammatory responses. Here, we evaluated the anti‐inflammatory role of LXA 4 , during the acute phase of zymosan‐induced arthritis, focusing on the modulation of ET‐1 expression and its effects. EXPERIMENTAL APPROACH The anti‐inflammatory effects of LXA 4 , BML‐111 (agonist of FPR2/ALX receptors) and acetylsalicylic acid (ASA) pre‐ and post‐treatments were investigated in a murine model of zymosan‐induced arthritis. Articular inflammation was assessed by examining knee joint oedema; neutrophil accumulation in synovial cavities; and levels of prepro‐ET‐1 mRNA, leukotriene (LT)B 4 , tumour necrosis factor (TNF)‐α and the chemokine KC/CXCL1, after stimulation. The direct effect of LXA 4 on ET‐1‐induced neutrophil activation and chemotaxis was evaluated by shape change and Boyden chamber assays respectively. KEY RESULTS LXA 4 , BML‐111 and ASA administered as pre‐ or post‐treatment inhibited oedema and neutrophil influx induced by zymosan stimulation. Zymosan‐induced preproET‐1 mRNA, KC/CXCL1, LTB 4 and TNF‐α levels were also decreased after LXA 4 pretreatment. In vitro , ET‐1‐induced neutrophil chemotaxis was inhibited by LXA 4 pretreatment. LXA 4 treatment also inhibited ET‐1‐induced oedema formation and neutrophil influx into mouse knee joints. CONCLUSION AND IMPLICATION LXA 4 exerted anti‐inflammatory effects on articular inflammation through a mechanism that involved the inhibition of ET‐1 expression and its effects." @default.
• W1818367061 created "2016-06-24" @default.
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• W1818367061 date "2010-07-07" @default.
• W1818367061 modified "2023-10-17" @default.
• W1818367061 title "Lipoxin A4 attenuates zymosan-induced arthritis by modulating endothelin-1 and its effects" @default.
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• W1818367061 doi "https://doi.org/10.1111/j.1476-5381.2010.00950.x" @default.
• W1818367061 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2992904" @default.
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