Regulation of CXCL1 chemokine and CSF3 cytokine levels in myometrial cells by the MAFF transcription factor

MAFF 转录因子对子宫肌层细胞中 CXCL1 趋化因子和 CSF3 细胞因子水平的调节

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作者:James Saliba, Baptiste Coutaud, Vera Solovieva, Fangshi Lu, Volker Blank

Abstract

Cytokines play key roles in a variety of reproductive processes including normal parturition as well as preterm birth. Our previous data have shown that MAFF, a member of the MAF family of bZIP transcription factors, is rapidly induced by pro-inflammatory cytokines in PHM1-31 myometrial cells. We performed loss-of-function studies in PHM1-31 cells to identify MAFF dependent genes. We showed that knockdown of MAFF significantly decreased CXCL1 chemokine and CSF3 cytokine transcript and protein levels. Using chromatin immunoprecipitation analyzes, we confirmed CXCL1 and CSF3 genes as direct MAFF targets. We also demonstrated that MAFF function in PHM1-31 myometrial cells is able to control cytokine and matrix metalloproteinase gene expression in THP-1 monocytic cells in a paracrine fashion. Our studies provide valuable insights into the MAFF dependent transcriptional network governing myometrial cell function. The data suggest a role of MAFF in parturition and/or infection-induced preterm labour through modulation of inflammatory processes in the microenvironment.

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