title: Progesterone suppresses interferon signaling by repressing TLR-7 and MxA expression in peripheral blood mononuclear cells of patients infected with hepatitis C virus.
abstract: This study aimed at investigating the effect of progesterone on interferon signaling pathways in peripheral blood mononuclear cells (PBMCs) of patients infected with hepatitis C virus (HCV). PBMCs were isolated from peripheral blood of 38 treatment-naïve HCV-infected patients, pooled, and stimulated with progesterone in the presence and absence of its receptor antagonist, mifepristone, along with interferon alpha (IFN-α) or imiquimod. Toll-like receptor (TLR) 7 and myxovirus resistance protein A (MxA) were quantified in PBMCs using RT-qPCR. Imiquimod alone or combined with progesterone did not change MxA expression in HCV-infected PBMCs. Progesterone decreased the inducing effect of IFN-α on TLR-7 expression in both males and females. Moreover, progesterone stimulation prior to IFN-α treatment attenuated the Jak/STAT pathway, which was reflected by decreased expression of MxA in females. Progesterone showed a negative impact on the IFN signaling pathway in HCV-infected PBMCs as it decreased the expression of TLR-7 in both genders, while MxA expression was decreased only in females.
authors.affiliation: The Molecular Pathology Research Group, Department of Pharmacology and Toxicology, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, Egypt.
authors.forename: Sara S
authors.initials: SS
authors.lastname: Tayel
authors.forename: Amal A
authors.initials: AA
authors.lastname: Helmy
authors.forename: Rasha
authors.initials: R
authors.lastname: Ahmed
authors.forename: Gamal
authors.initials: G
authors.lastname: Esmat
authors.forename: Nabila
authors.initials: N
authors.lastname: Hamdi
authors.forename: Ahmed Ihab
authors.initials: AI
authors.lastname: Abdelaziz
mesh_terms: D000328:Adult; D005260:Female; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors*; D016174:Hepacivirus / Q000254:growth & development / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007372:Interferons / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology / Q000821:virology; D008297:Male; D008875:Middle Aged; D064547:Myxovirus Resistance Proteins; D011374:Progesterone / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D051199:Toll-Like Receptor 7 / Q000037:antagonists & inhibitors*; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; C495348:TLR7 protein, human; D051199:Toll-Like Receptor 7; D011374:Progesterone; D007372:Interferons; D019204:GTP-Binding Proteins