Involvement of nuclear factor-kappaB in macrophage migration inhibitory factor gene transcription up-regulation induced by interleukin- 1 beta in ectopic endometrial cells

Fertil Steril. 2009 May;91(5 Suppl):2148-56. doi: 10.1016/j.fertnstert.2008.05.017. Epub 2008 Aug 16.


Objective: To investigate the involvement of the nuclear factor (NF)-kappaB in the interleukin (IL)-1 beta-mediated macrophage migration inhibitory factor (MIF) gene activation.

Design: Prospective study.

Setting: Human reproduction research laboratory.

Patient(s): Nine women with endometriotic lesions.

Intervention(s): Endometriotic lesions were obtained during laparoscopic surgery.

Main outcome measure(s): The MIF protein secretion was analyzed by ELISA, MIF mRNA expression by quantitative real-time polymerase chain reaction (PCR), NF-kappaB translocation into the nucleus by electrophoresis mobility shift assay, I kappaB phosphorylation and degradation by Western blot, and human MIF promoter activity by transient cell transfection.

Result(s): This study showed a significant dose-dependent increase of MIF protein secretion and mRNA expression, the NF-kappaB translocation into the nucleus, I kappaB phosphorylation, I kappaB degradation, and human MIF promoter activity in endometriotic stromal cells in response to IL-1 beta. Curcumin (NF-kappaB inhibitor) significantly inhibited all these IL-1 beta-mediated effects. Analysis of the activity of deletion constructs of the human MIF promoter and a computer search localized two putative regulatory elements corresponding to NF-kappaB binding sites at positions -2538/-2528 bp and -1389/-1380 bp.

Conclusion(s): This study suggests the involvement of the nuclear transcription factor NF-kappaB in MIF gene activation in ectopic endometrial cells in response to IL-1 beta and identifies a possible pathway of endometriosis-associated inflammation and ectopic cell growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Culture Techniques
  • Endometriosis / genetics*
  • Endometriosis / pathology
  • Female
  • Humans
  • Interleukin-1beta / pharmacology*
  • Macrophage Migration-Inhibitory Factors / genetics*
  • NF-kappa B / physiology*
  • Pregnancy
  • Pregnancy, Ectopic / genetics
  • RNA, Messenger / genetics
  • Transcription, Genetic / drug effects*
  • Up-Regulation / drug effects*


  • Interleukin-1beta
  • Macrophage Migration-Inhibitory Factors
  • NF-kappa B
  • RNA, Messenger