title: Progesterone inhibits Toll-like receptor 4-mediated innate immune response in macrophages by suppressing NF-kappaB activation and enhancing SOCS1 expression.
abstract: Although progesterone has been recognized as essential for the establishment and maintenance of pregnancy, this steroid hormone has been implicated to have a functional role in immune response, mainly at concentrations commensurate with pregnancy. However, the underlying mechanisms remain to be fully understood. Here we present the evidences that progesterone inhibited immune response to lipopolysaccharide (LPS) and CpG oligodeoxynucleotides (CpG ODNs) through modulating Toll-like receptor (TLR) signaling. Pretreatment with progesterone can significantly inhibit TLR4 and TLR9-triggered IL-6 and nitric oxide (NO) production in macrophages. Furthermore, we found that progesterone can significantly inhibit LPS-induced nitric oxide synthesis (iNOS), TLR4 expression and nuclear factor-kappaB (NF-kappaB) activation. Consistently, as a negative feedback inhibitor, the expression of suppressor of cytokine signaling (SOCS1) protein was up-regulated by progesterone in LPS-stimulated macrophages. These results support the concept that progesterone might inhibit innate immune response by suppressing NF-kappaB activation and enhancement of SOCS1 expression, providing a possible mechanistic explanation for the function of progesterone in regulating innate immune responses.
authors.affiliation: Laboratory of Reproduction and Genetics, School of Medicine, Zhejiang University, Hangzhou 310058, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Su
authors.forename: Yixi
authors.initials: Y
authors.lastname: Sun
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; D018899:CpG Islands; D015536:Down-Regulation; D025461:Feedback, Physiological; D007113:Immunity, Innate / Q000187:drug effects; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology*; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000276:immunology / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects; D015854:Up-Regulation
chemical_list: D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D051197:Toll-Like Receptor 4; D009569:Nitric Oxide; D011374:Progesterone; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse