Medroxyprogesterone Acetate Differentially Regulates Interleukin (IL)-12 and IL-10 in a Human Ectocervical Epithelial Cell Line in a Glucocorticoid Receptor (GR)-dependent Manner

摘要: Medroxyprogesterone acetate (MPA), designed to mimic the actions of endogenous hormone progesterone (P4), is extensively used by women as a contraceptive and in replacement therapy. However, little known about steroid receptor-mediated molecular mechanisms action MPA female genital tract. In this study, we investigated regulation pro-inflammatory cytokine, interleukin (IL)-12, anti-inflammatory cytokine IL-10, versus P4, an vitro cell culture model ectocervical environment. This study shows that P4 significantly increase expression IL-12p40 IL-12p35 genes, whereas IL-10 gene suppressed dose-dependent manner. Moreover, these effects were abrogated when reducing glucocorticoid receptor (GR) levels with siRNA. Using combination chromatin immunoprecipitation (ChIP), siRNA, re-ChIP assays, show recruitment P4- MPA-bound GR promoter requires CCAAT enhancer-binding protein (C/EBP)-β nuclear factor κB (NFκB), although signal transducer activator transcription (STAT)-3. These results suggest both may modulate inflammation ectocervix via genomic mechanism.