title: miR-155 mediates suppressive effect of progesterone on TLR3, TLR4-triggered immune response.
abstract: It has been demonstrated that progesterone has immune suppressive properties and can inhibit Toll-like receptor 4 (TLR4)-triggered immune response. Multiple microRNAs are induced in innate immune cells, among them miR-155, miR-146a and miR-21 are particularly ubiquitous. In this study, we investigated the potential roles of miR-155 in progesterone-mediated regulation of innate immune responses. We found that progesterone pre-treatment suppressed LPS- and poly(I:C)-induced miR-155 expression in macrophages. Increasing the activity of miR-155, significantly attenuated the progesterone's inhibition on LPS-induced IL-6 as well as LPS- and poly(I:C)-induced IFN-β expression in macrophages. Furthermore, we demonstrated that progesterone up-regulated LPS-induced SOCS1 expression while overexpression of miR-155 inhibited SOCS1 expression. In conclusion, the present study has demonstrated that progesterone suppresses TLRs-triggered immune response by regulating miR-155, and the decreased miR-155 contributes to inhibit TLR-induced IL-6 and IFN-β via increased SOCS1 expression.
authors.affiliation: Institute of Reproduction and Genetics, School of Medicine, Zhejiang University, 866 Yuhang Tang Road, Hangzhou 310058, China.
authors.forename: Yixi
authors.initials: Y
authors.lastname: Sun
authors.forename: Jiaojiao
authors.initials: J
authors.lastname: Cai
authors.forename: Feng
authors.initials: F
authors.lastname: Ma
authors.forename: Pingping
authors.initials: P
authors.lastname: Lü
authors.forename: Hefeng
authors.initials: H
authors.lastname: Huang
authors.forename: Jun
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000818:Animals; D002460:Cell Line; D005786:Gene Expression Regulation / Q000276:immunology; D007113:Immunity, Innate; D016899:Interferon-beta / Q000096:biosynthesis / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology*; D011070:Poly I-C / Q000494:pharmacology; D011374:Progesterone / Q000276:immunology / Q000494:pharmacology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D051196:Toll-Like Receptor 3 / Q000235:genetics / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology*
chemical_list: D015850:Interleukin-6; D008070:Lipopolysaccharides; D035683:MicroRNAs; C532623:Mirn155 microRNA, mouse; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; C519703:TLR3 protein, mouse; C493487:Tlr4 protein, mouse; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D011374:Progesterone; D016899:Interferon-beta; D011070:Poly I-C