ERB-041, a selective ER beta agonist, inhibits iNOS production in LPS-activated peritoneal macrophages of endometriosis via suppression of NF-kappaB activation

Mol Immunol. 2009 Jul;46(11-12):2413-8. doi: 10.1016/j.molimm.2009.04.014. Epub 2009 May 17.


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.

Conclusion: 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.

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Cells, Cultured
  • Endometriosis / enzymology*
  • Endometriosis / immunology
  • Endometriosis / pathology
  • Estrogen Receptor beta / agonists*
  • Estrogen Receptor beta / metabolism
  • Extracellular Signal-Regulated MAP Kinases / physiology
  • Female
  • Humans
  • Lipopolysaccharides / pharmacology
  • Macrophage Activation / drug effects
  • Macrophages, Peritoneal / drug effects*
  • Macrophages, Peritoneal / enzymology
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / metabolism
  • Nitric Oxide Synthase Type II / antagonists & inhibitors
  • Nitric Oxide Synthase Type II / metabolism*
  • Oxazoles / pharmacology*
  • Signal Transduction


  • Anti-Inflammatory Agents, Non-Steroidal
  • ERB 041
  • Estrogen Receptor beta
  • Lipopolysaccharides
  • NF-kappa B
  • Oxazoles
  • Nitric Oxide Synthase Type II
  • Extracellular Signal-Regulated MAP Kinases