title: Effects of 17β-estradiol on the release of monocyte chemotactic protein-1 and MAPK activity in monocytes stimulated with peritoneal fluid from endometriosis patients.
abstract: OBJECTIVE
  Hormones and inflammation have been implicated in the pathological process of endometriosis; therefore, we investigated the combined effects of 17β-estradiol (E2) and peritoneal fluid obtained from patients with endometriosis (ePF) or a control peritoneal fluid (cPF) obtained from patients without endometriosis on the release of monocyte chemotactic protein-1 (MCP-1) by monocytes and the role of signaling pathways.
  
  
  METHODS
  Monocytes were cultured with ePF and cPF in the presence of E2; the MCP-1 levels in the supernatants were then measured by ELISA. In addition, mitogen activated protein kinase (MAPK) activation was measured by Western blotting of phosphorylated proteins.
  
  
  RESULTS
  E2 down-regulated MCP-1 release by lipopolysaccharide- or cPF-treated monocytes, but failed to suppress its release by ePF-treated monocytes. The release of MCP-1 by ePF- and cPF-treated monocytes was efficiently abrogated by p38 mitogen activated protein kinase (MAPK) inhibitors; however, the MCP-1 release by cPF-treated monocytes, but not by ePF-treated monocytes, was blocked by a MAPK kinase inhibitor. In addition, ePF and cPF induced the phosphorylation of extracellular stress regulated kinase (ERK)1/2, p38 MAPK and c-Jun N-terminal kinase (JNK). E2 decreased the phosphorylation of p38 MAPK, but not ERK1/2 in ePF-treated monocytes; however, E2 decreased the phosphorylation of p38 MAPK, ERK1/2 and JNK in cPF-treated monocytes.
  
  
  CONCLUSIONS
  The ability of E2 to modulate MCP-1 production is impaired in ePF-treated monocytes, which may be related to regulation of MAPK activity. These findings suggest that the failure of E2 to suppress ePF-treated production of MCP-1 may be involved in the pathogenesis of endometriosis.
authors.affiliation: Department of Obstetrics and Gynecology, Medical Research Institute, Pusan National University, Busan, Korea.
authors.forename: Dong-Hyung
authors.initials: DH
authors.lastname: Lee
authors.forename: Seung-Chul
authors.initials: SC
authors.lastname: Kim
authors.forename: Jong-Kil
authors.initials: JK
authors.lastname: Joo
authors.forename: Hwi-Gon
authors.initials: HG
authors.lastname: Kim
authors.forename: Young-Jin
authors.initials: YJ
authors.lastname: Na
authors.forename: Jong-Young
authors.initials: JY
authors.lastname: Kwak
authors.forename: Kyu-Sup
authors.initials: KS
authors.lastname: Lee
mesh_terms: D001202:Ascitic Fluid / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D018932:Chemokine CCL2 / Q000378:metabolism*; D004715:Endometriosis / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D020935:MAP Kinase Signaling System; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D010049:Ovarian Diseases / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D018932:Chemokine CCL2; D004958:Estradiol; D020928:Mitogen-Activated Protein Kinases