title: Lipoxin A4 suppresses the development of endometriosis in an ALX receptor-dependent manner via the p38 MAPK pathway.
abstract: OBJECTIVE
  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 A4 (LXA4 ) suppresses the development of endometriosis.
  
  
  METHODS
  Primary endometriotic stromal cells (ESCs) were treated with IL-1β, or pre-incubated with LXA4 before incubation with IL-1β. The LXA4 receptor (ALX receptor) antagonist Boc-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.
  
  
  RESULTS
  Decreased levels of LXA4 and 15-LOX-2 expression but increased expression of AXL receptors were observed in endometriotic tissues. LXA4 inhibited the release of inflammatory factors and phosphorylation of p38 MAPK in IL-1β-induced ESCs, an effect mediated by ALX receptors. LXA4 inhibited the proliferation of ESCs, as indicated by reduced DNA replication, caused G0 /G1 phase cell cycle arrest and down-regulated the expression of proliferating cell nuclear antigen in ESCs. LXA4 also attenuated the invasive activity of ESCs mainly by suppressing the expression and activity of MMP-9. In vivo, we further confirmed that LXA4 could inhibit the progression of endometriosis by acting as an anti-inflammatory.
  
  
  CONCLUSIONS
  LXA4 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.
authors.affiliation: State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, China.
authors.forename: Rongfeng
authors.initials: R
authors.lastname: Wu
authors.forename: Weidong
authors.initials: W
authors.lastname: Zhou
authors.forename: Shuo
authors.initials: S
authors.lastname: Chen
authors.forename: Yan
authors.initials: Y
authors.lastname: Shi
authors.forename: Lin
authors.initials: L
authors.lastname: Su
authors.forename: Maobi
authors.initials: M
authors.lastname: Zhu
authors.forename: Qionghua
authors.initials: Q
authors.lastname: Chen
authors.forename: Qingxi
authors.initials: Q
authors.lastname: Chen
mesh_terms: D000818:Animals; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004715:Endometriosis / Q000378:metabolism*; D004717:Endometrium / Q000378:metabolism; D005260:Female; D020868:Gene Silencing; D006801:Humans; D044045:Lipoxins / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D008807:Mice, Inbred BALB C; D044067:Receptors, Lipoxin / Q000378:metabolism*; D017154:Stromal Cells / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D016207:Cytokines; D044045:Lipoxins; D044067:Receptors, Lipoxin; C040527:lipoxin A4; C458528:ALOX15B protein, human; D001093:Arachidonate 15-Lipoxygenase; D048051:p38 Mitogen-Activated Protein Kinases; D020780:Matrix Metalloproteinase 9