Medroxyprogesterone Acetate Differentially Regulates Interleukin (IL)-12 and IL-10 in a Human Ectocervical Epithelial Cell Line in a Glucocorticoid Receptor (GR)-dependent Manner
Medroxyprogesterone Acetate Differentially Regulates Interleukin (IL)-12 and IL-10 in a Human Ectocervical Epithelial Cell Line in a Glucocorticoid Receptor (GR)-dependent Manner
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DOI：
10.1074/jbc.m114.587311
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发表时间：
2014-11-07
影响因子：
4.8
通讯作者：
Africander, Donita
中科院分区：
文献类型：
--
作者：
Louw-du Toit, Renate;Hapgood, Janet P.;Africander, Donita
Medroxyprogesterone acetate (MPA), designed to mimic the actions of the endogenous hormone progesterone (P-4), is extensively used by women as a contraceptive and in hormone replacement therapy. However, little is known about the steroid receptor-mediated molecular mechanisms of action of MPA in the female genital tract. In this study, we investigated the regulation of the pro-inflammatory cytokine, interleukin (IL)-12, and the anti-inflammatory cytokine IL-10, by MPA versus P-4, in an in vitro cell culture model of the female ectocervical environment. This study shows that P-4 and MPA significantly increase the expression of the IL-12p40 and IL-12p35 genes, whereas IL-10 gene expression is suppressed in a dose-dependent manner. Moreover, these effects were abrogated when reducing the glucocorticoid receptor (GR) levels with siRNA. Using a combination of chromatin immunoprecipitation (ChIP), siRNA, and re-ChIP assays, we show that recruitment of the P-4- and MPA-bound GR to the IL-12p40 promoter requires CCAAT enhancer-binding protein (C/EBp)-beta and nuclear factor kappa B (NF kappa B), although recruitment to the IL-10 promoter requires signal transducer and activator of transcription (STAT)-3. These results suggest that both P-4 and MPA may modulate inflammation in the ectocervix via this genomic mechanism.
