title: ERB-041, a selective ER beta agonist, inhibits iNOS production in LPS-activated peritoneal macrophages of endometriosis via suppression of NF-kappaB activation.
abstract: OBJECTIVE
  The aim of the present study was to assess the anti-inflammatory effects of selective ER beta (ER beta) agonist on lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS) production in peritoneal macrophages (PMs) of endometriosis (EMS).
  
  
  METHODS
  ER alpha (ER alpha) and ER beta expressions in PMs were analyzed by RT-PCR and immunoblot. The PMs of endometriosis were exposed to increasing concentrations of ER beta agonist ERB-041 over a period from 0.5 to 8h before stimulation with LPS and the levels of iNOS protein were evaluated by immunoblot. Subsequently, the PMs were pretreated with vehicle, ERB-041 or ER alpha agonist PPT before exposing to LPS. iNOS expression, p65 protein and active extracellular signal-regulated kinases (ERKs) level accumulated in the nuclear were detected by immunoblot. For experiment investigating the role of ERKs in LPS-induced iNOS expression, the PMs were pretreated with U0126, a specific ERK inhibitor, for 60 min before LPS treatment and iNOS expression was detected by immunoblot.
  
  
  RESULTS
  The PMs of EMS expressed ER beta to a greater extent compared with normal women. Pretreatment the PMs with ERB-041 resulted in a significant inhibition of LPS-induced iNOS expression and NF-kappaB activation by preventing its nuclear translocation. The ERKs pathway was involved in the LPS-induced iNOS production and was not repressed by the activation of ERs.
  
  
  CONCLUSIONS
  The inhibitory effect of ER beta agonist on LPS-induced iNOS production in PMs of EMS is likely mediated via repressing of nuclear factor-kappa B (NF-kappaB) but not ERKs signaling pathways.
authors.affiliation: Department of Gynecology, First Affiliated Hospital of Nanjing Medical University, 368 North-Jiangdong Road, Nanjing, China. xiuli_2266@163.com
authors.forename: Wang
authors.initials: W
authors.lastname: Xiu-li
authors.forename: Cheng
authors.initials: C
authors.lastname: Wen-jun
authors.forename: Dai
authors.initials: D
authors.lastname: Hui-hua
authors.forename: Han
authors.initials: H
authors.lastname: Su-ping
authors.forename: Fu
authors.initials: F
authors.lastname: Shi-long
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002478:Cells, Cultured; D004715:Endometriosis / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D047629:Estrogen Receptor beta / Q000819:agonists* / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D005260:Female; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000201:enzymology; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010080:Oxazoles / Q000494:pharmacology*; D015398:Signal Transduction
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C478102:ERB 041; D047629:Estrogen Receptor beta; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010080:Oxazoles; D052247:Nitric Oxide Synthase Type II; D048049:Extracellular Signal-Regulated MAP Kinases