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Hum. Reprod. Advance Access published online on October 6, 2005

Human Reproduction, doi:10.1093/humrep/dei315
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© The Author 2005. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received November 12, 2004
Revised August 2, 2005
Accepted August 22, 2005

Article

Tumour necrosis factor-{alpha} up-regulates macrophage migration inhibitory factor expression in endometrial stromal cells via the nuclear transcription factor NF-{kappa}B

W.G. Cao 1, M. Morin 1, V. Sengers 1, C. Metz 2, T. Roger 3, R. Maheux 1, and A. Akoum 1*

1 Unité d’endocrinologie de la reproduction, Centre de Recherche, Hôpital Saint-François d’Assise, Centre Hospitalier Universitaire de Québec, Faculté de Médecine, Université Laval, Québec, Canada
2 Institute for Medical Research at North Shore-LIJ, NY, USA
3 Service des Maladies Infectieuses, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland

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


   Abstract

BACKGROUND: A series of controlled changes including proliferation, secretion and menstrual shedding occur in the human endometrium during every normal menstrual cycle. Macrophage migration inhibitory factor (MIF), a multifunctional cytokine with numerous proinflammatory, immunomodulatory and angiogenic properties, appears to be expressed in the human endometrium and to follow a regulated cycle phase-dependent expression, but the mechanisms underlying endometrial MIF expression remain to be fully elucidated. METHODS AND RESULTS: Results from enzyme-linked immunosorbent assay (ELISA) demonstrated a significant dose- and time-dependent increase in MIF secretion by human endometrial cells in response to tumour necrosis factor-alpha (TNF-{alpha}) (0.1-100 ng/ml). This increase was also observed at the mRNA level as shown by reverse transcription (RT)-PCR. Curcumin (10-8 mol/l), a known nuclear factor (NF)-{kappa}B inhibitor, inhibited the TNF-{alpha}-induced pI{kappa}B phosphorylation as shown by western blotting, NF-{kappa}B translocation into the nucleus as shown by electrophoretic mobility shift assay, and MIF synthesis and secretion as measured by ELISA and RT-PCR. The expression of a dominant-negative NF-{kappa}B inhibitor (I{kappa}B) significantly decreased the TNF-{alpha}-induced MIF promoter activity as analysed by transient cell transfection. CONCLUSIONS: These results indicate clearly that TNF-{alpha} up-regulates the expression of MIF in endometrial stromal cells. This took place possibly through NF-{kappa}B activation, and may play an important role in the physiology of the human endometrium.

Keywords: endometrium/MIF/NF-{kappa}B/TNF-{alpha}.
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