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

Véronique Veillat, Veillat V, Lavoie CH, Catherine Herrmann Lavoie, Catherine Lavoie, Metz CN, Christine N. Metz, Thierry Roger, Yves Labelle, Labelle Y, Ali Akoum, Akoum A
Fertility and sterility · 2008 · vol. 91(5) , pp. 2148–2156 · doi:10.1016/j.fertnstert.2008.05.017 · PMID:18710704 · W1996118541
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Interleukin-1β up-regulates macrophage migration inhibitory factor gene transcription in ectopic endometrial cells through the activation of nuclear factor-κB.

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Abstract

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.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Interleukin-1beta Macrophage Migration-Inhibitory Factors NF-kappa B Transcription, Genetic Up-Regulation Cell Culture Techniques Cell Culture Techniques Endometriosis Endometriosis Endometriosis Female Female Humans Humans Interleukin-1beta Interleukin-1beta Macrophage Migration-Inhibitory Factors Macrophage Migration-Inhibitory Factors NF-kappa B

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