Hum. Reprod. Advance Access originally published online on October 6, 2005
Human Reproduction 2006 21(2):421-428; doi:10.1093/humrep/dei315
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Tumour necrosis factor-
up-regulates macrophage migration inhibitory factor expression in endometrial stromal cells via the nuclear transcription factor NF-
B
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 and 3 Service des Maladies Infectieuses, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
4 To whom correspondence should be addressed at: Laboratoire d’Endocrinologie de la Reproduction, Centre de Recherche, Hôpital Saint-François d’Assise, 10 rue de l’Espinay, Local D0-711, Québec, Québec, Canada G1L 3L5. E-mail: ali.akoum{at}crsfa.ulaval.ca
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-
) (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)-
B inhibitor, inhibited the TNF--induced pIB phosphorylation as shown by western blotting, NF-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-B inhibitor (IB) significantly decreased the TNF--induced MIF promoter activity as analysed by transient cell transfection. CONCLUSIONS: These results indicate clearly that TNF- up-regulates the expression of MIF in endometrial stromal cells. This took place possibly through NF-B activation, and may play an important role in the physiology of the human endometrium.
Key words:
endometrium/MIF/NF-B/TNF-
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