The Molecular Mechanism Of The Inhibitory Effects Of Lipoxin A₄on Endometriosis

Objective:To study the relationship between LXA4and ER, PR. To explore the influence of LXA4on the expression of ER and PR, and the regulatory effects of LXA4on ER-p38MAPK cross talk.Methods:The expression of LXA4, ER and PR in normal and ectopic endometrium was measured by Enzyme-linked immunosorbent assay, real-time quantitative PCR and immunohistochemistry. The mRNA levels of ER, PR, TNF-a and IL-6were quantified by qRT-PCR. p38MAPK was evaluated by Western blotting and immunohistochemistry. ERE transcriptional activity was detected by luciferase report gene. Effect of LXA4on proliferation of ESCs was detected by MTS assay and EdU incorporation.Results:In normal endometrium, the mRNA expressions of ERa and ERP change periodically in the proliferative phase and secretory phase, while the expression of ERa and ERβ in ectopic endometrium was independent of the menstrual cycle. LXA4expression level decreased in ectopic tissue, as well as ERa and PR. While the expression of ERP increased in ectopic endometrium, compared to control subjects. Administering LXA4could augment ERβ expression in ESCs and the ERβ specific agonist------DPN could inhibit the phosphorylation of p38MAPK. Moreover, LXA4inhibit E2-induced phosphorylation of p38MAPK and downregulate the expression of TNF-a and IL-6.Conclusions:Our findings indicate that LXA4regulates ERβ expression and inhibits E2-induced phosphorylation of p38MAPK, very likely through ERP in ESCs.