lipoxin a-4

Lipoxin A4 (LXA4) 是一种内源性脂氧合酶衍生的类花生酸介质，具有抗炎作用。Lipoxin A4 通过抑制 Nrf2 来减弱 MSU 晶体诱导的 NLRP3 炎症小体激活，通过 FPR2-IRF 途径调节 M1 M2 巨噬细胞极化。Lipoxin 抑制氧化应激和炎症。

Lipoxin A4 methyl ester (LXA4 methyl ester) is a more lipid soluble, prodrug formulation of the transcellular metabolite LXA4. LXA4 is a trihydroxy fatty acid containing a conjugated tetraene, produced by the metabolism of 15-HETE or 15-HpETE with human leukocytes.[1] LXA4 is equipotent to leukotriene B4 (LTB4) in inducing superoxide generation in human neutrophils at 0.1 μM.[2] LXA4 is associated with several other biological functions including leukocyte activation, chemotaxis effects, natural killer cell inhibition, and monocyte migration and adhesion.[2],[3],[4]

Lipid-derived lipoxins are produced at the site of vascular and mucosal inflammation where they down-regulate polymorphonuclear leukocyte recruitment and function. 15(R)-Lipoxin A4 (15(R)-LXA4) is derived from the aspirin-triggered formation of 15(R)-HETE from arachidonic acid. [1] [2] 15(R)-LXA4 inhibits LTB4-induced chemotaxis, adherence, and transmigration of neutrophils with twice the potency of LXA4 demonstrating activity in the nM range.[2] [3] The anti-inflammatory effects of aspirin may be ascribed in part to the ability of 15(R)-LXA4 to regulate leukocyte function.[4] 15(R)-LXA4 is reported to promote resolution of inflammation in LPS-treated stromal cells derived from intermediate-stage diseased supraspinatus tendons as evidenced by increased expression of the STAT-6 pathway target genes, ALOX15 and CD206.[5]

The lipoxins are trihydroxy fatty acids containing a 7,9,11,13-conjugated tetraene. Lipoxin A4 (LXA4) was first described as a metabolite of 15-HpETE and or 15-HETE when added in vitro to isolated human leukocytes. The material obtained in this manner consists of at least four distinct isomers: 5(S), 6(S); 5(S), 6(R); and the 11-trans and 11-cis isomers of each of these. 6(S)-LXA4 is one of the original four metabolites first identified by Serhan, Nicolaou, and Samuelsson. It was considered to be an artifact by these authors because it lacked the potency of the 5(S),6(R) isomer with respect to contraction of isolated guinea pig lung parenchymal strips. It has not been possible to isolate natural LXA4 from humans or other mammals in amounts sufficient for determination of absolute stereochemistry. Most authors refer to LXA4 as the 5(S)