Lipoxin A4 regulates expression of the estrogen receptor and inhibits 17β-estradiol induced p38 mitogen-activated protein kinase phosphorylation in human endometriotic stromal cells

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Lipoxin A4 modulates estrogen receptor expression and reduces 17β-estradiol-stimulated p38 MAPK phosphorylation in human endometriotic stromal cells.

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Abstract

OBJECTIVE: To study the role of lipoxin A4 (LXA4) in endometriosis. DESIGN: Molecular analysis in human samples and primary human endometriotic stromal cells (ESCs). SETTING: University hospital. PATIENT(S): Forty-nine premenopausal women (30 patients with endometriosis and 19 controls). INTERVENTION(S): Normal and ectopic endometrial biopsies obtained during surgery performed during the proliferative phase of the menstrual cycle; ESCs used for in vitro studies. MAIN OUTCOME MEASURE(S): Levels of LXA4 measured by enzyme-linked immunosorbent assay (ELISA); mRNA levels of the estrogen receptor (ER), progestogen receptor (PR), tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) quantified by quantitative reverse-transcription polymerase chain reaction (qRT-PCR); and p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation evaluated by Western blotting. RESULT(S): The LXA4 expression level decreased in ectopic tissue as well as ERα and PR, although the expression of ERβ increased in ectopic endometrium compared with the controls. Investigations with correlation analysis revealed the expression of LXA4 was positively correlated with ERα and negatively correlated with ERβ in vivo. Moreover, administering LXA4 could augment ERβ expression in ESCs and inhibit the 17β-estradiol-induced phosphorylation of p38 MAPK very likely through ERβ. CONCLUSION(S): Our findings indicate that LXA4 regulates ERβ expression and inhibits 17β-estradiol-induced phosphorylation of p38 MAPK, very likely through ERβ in ESCs.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Endometrium Estradiol Estrogen Receptor beta Lipoxins p38 Mitogen-Activated Protein Kinases Stromal Cells Adult Adult Case-Control Studies Case-Control Studies Cells, Cultured Cells, Cultured Endometriosis Endometriosis Endometriosis Endometrium Endometrium Enzyme Activation Enzyme Activation

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