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BOR - Papers in Press, published online ahead of print May 18, 2005.
Biol Reprod 2005, 10.1095/biolreprod.104.038331
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Submitted November 22, 2004
Returned for revision December 21, 2004
Accepted May 9, 2005

Female Reproductive Tract


Stimulation of Macrophage Migration Inhibitory Factor Expression in Endometrial Stromal Cells by Interleukin 1,{beta} Involving the Nuclear Transcription Factor NF{kappa}B

W-G. Cao , M. Morin , C. Metz , R. Maheux , and A. Akoum *

* To whom correspondence should be addressed. E-mail: ali.akoum{at}crsfa.ulaval.ca.

Abstract
Endometriosis, the ectopic development of endometrial tissue, is, at least peritoneal endometriosis, believed to result from tubal reflux of menstrual tissue. The release of cytokines and growth factors by refluxed endometrial cells in response to peritoneal inflammatory stimuli may enhance the capability of endometrial cells to implant and grow into the peritoneal host tissue. Herein we report that interleukin 1 (IL1), a major pro-inflammatory cytokine which is overproduced by endometriosis women-derived peritoneal macrophages and found in elevated concentrations in the peritoneal fluid of endometriosis patients, stimulates the synthesis and the secretion of macrophage migration inhibitory factor (MIF) by human endometrial stromal cells. IL1B (0.1-100 ng/ml) exerted a dose- and time-dependent effects of MIF protein secretion and mRNA synthesis, as shown by enzyme-linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR), respectively. IL1B appeared to induce MIF gene transcription via the nuclear transcription factor NF{kappa}B, as shown by electrophoretic mobility shift assay (EMSA) and Western blot analysis of I{kappa}B phosphorylation. Curcumin (10-8 M), which is known for inhibiting NF{kappa}B activation, inhibited IL1B-induced MIF secretion as well as NF{kappa}B nuclear translocation and DNA binding. Taken together these findings clearly show that IL1B up-regulates the expression of MIF in endometrial stromal cells in vitro and acts via NF{kappa}B. This may play an important role in the physiology of the human endometrium and the pathophysiology of endometriosis considering the immunomodulatory properties of MIF as well as its role in cell growth, angiogenesis and tissue remodeling.

Key words: Female Reproductive Tract • Cytokines • Menstrual cycle • Uterus


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