Tumour necrosis factor-α up-regulates macrophage migration inhibitory factor expression in endometrial stromal cells via the nuclear transcription factor NF-κB

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-α) (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)-κB inhibitor, inhibited the TNF-α-induced pIκB phosphorylation as shown by western blotting, NF-κB 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-κB inhibitor (IκB) significantly decreased the TNF-α-induced MIF promoter activity as analysed by transient cell transfection. Conclusions: These results indicate clearly that TNF-α up-regulates the expression of MIF in endometrial stromal cells. This took place possibly through NF-κB activation, and may play an important role in the physiology of the human endometrium. © The Author 2005. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.