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Lipoxin A 4 suppresses the development of endometriosis in an ALX receptor‐dependent manner via the p38 MAPK pathway
Author(s) -
Wu Rongfeng,
Zhou Weidong,
Chen Shuo,
Shi Yan,
Su Lin,
Zhu Maobi,
Chen Qionghua,
Chen Qingxi
Publication year - 2014
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.12816
Subject(s) - receptor , stromal cell , mapk/erk pathway , endometriosis , p38 mitogen activated protein kinases , inflammation , chemistry , microbiology and biotechnology , cell growth , cancer research , phosphorylation , biology , endocrinology , medicine , immunology , biochemistry
Background and Purpose Lipoxins can function as endogenous ‘breaking signals’ in inflammation and play important roles in the progression of endometriosis. In this study, we further investigated the molecular mechanism by which lipoxin A 4 ( LXA 4 ) suppresses the development of endometriosis. Experimental Approach Primary endometriotic stromal cells ( ESCs ) were treated with IL ‐1β, or pre‐incubated with LXA 4 before incubation with IL ‐1β. The LXA 4 receptor ( ALX receptor) antagonist B oc‐2 and gene‐silencing approaches were used to study the involvement of the ALX receptor in anti‐inflammatory signalling responses in ESCs . An animal model of endometriosis was induced in BALB /c mice by i.p. injection of an endometrium‐rich fragment. Key Results Decreased levels of LXA 4 and 15‐ LOX ‐2 expression but increased expression of AXL receptors were observed in endometriotic tissues. LXA 4 inhibited the release of inflammatory factors and phosphorylation of p38 MAPK in IL ‐1β‐induced ESCs , an effect mediated by ALX receptors. LXA 4 inhibited the proliferation of ESCs , as indicated by reduced DNA replication, caused G 0 / G 1 phase cell cycle arrest and down‐regulated the expression of proliferating cell nuclear antigen in ESCs . LXA 4 also attenuated the invasive activity of ESCs mainly by suppressing the expression and activity of MMP ‐9. In vivo , we further confirmed that LXA 4 could inhibit the progression of endometriosis by acting as an anti‐inflammatory. Conclusions and Implications LXA 4 exerted anti‐inflammatory, anti‐proliferative and anti‐invasive effects on endometriosis through a mechanism that involved down‐regulating the activities of p38 MAPK , which was mediated by ALX receptors.