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]
Reference:
[1]. Clària, J., Lee, M.H., and Serhan, C.N. Aspirin-triggered lipoxins (15-epi-LX) are generated by the human lung adenocarcinoma cell line (A549)-neutrophil interactions and are potent inhibitors of cell proliferation. Molecular Medicine 2, 583-596 (1996).
[2]. Clària, J., and Serhan, C.N. Aspirin triggers previously undescribed bioactive eicosanoids by human endothelial cell-leukocyte interactions. PNAS USA 92(21), 9475-9479 (1995).
[3]. Fierro, I.M., Colgan, S.P., Bernasconi, G., et al. Lipoxin A4 and aspirin-triggered 15-epi-lipoxin A4 inhibit human neutrophil migration: Comparisons between synthetic 15 epimers in chemotaxis and transmigration with microvessel endothelial cells and epithelial cells. J. Immunol. 170(5), 2688-2694 (2003).
[4]. Chiang, N., Bermudez, E.A., Ridker, P.M., et al. Aspirin triggers antiinflammatory 15-epi-lipoxin A4 and inhibits thromboxane in a randomized human trial. Proceedings of the National Academy of Sciences of the United States of America 101(42), 15178-15183 (2004).
[5]. Dakin, S.G., Martinez, F.O., Yapp, C., et al. Inflammation activation and resolution in human tendon disease. Sci.Transl.Med. 7(311), (2015).