title: Tamoxifen downregulates MxA expression by suppressing TLR7 expression in PBMCs of males infected with HCV.
abstract: Gender discrepancies in immune response to HCV infections and during HCV therapy exist and previous findings including those from this research team indicate the female sex hormone, 17β-estradiol (E2), to be one probable cause of such inconsistencies. Also, it was recently demonstrated that estrogen receptor modulator Tamoxifen (TAM) exerts an upmodulating/enhancing effect on the TLR7 and JAK-STAT pathways in PBMCs of premenopausal females infected with HCV. Pursuing this work, a discrepancy was noticed in the results from male patients, therefore this study aimed to determine whether the effects of TAM previously observed in the PBMCs of women would hold true in PBMCs from males infected with HCV. Isolated PBMCs were pooled and relative expression of the TLR7 was quantified using RTqPCR. Sets of PBMCs were treated with exogenous interferon alpha (IFNα) or the TLR7 ligand, Imiquimod; these stimulations were performed with and without E2 and TAM pretreatment and the relative gene expressions of TLR7 and MxA were measured. Pretreatment with E2 and IFNα downregulated TLR7 (**P = 0.0080) and TAM further decreased this expression significantly (*P = 0.0284). TAM pretreatment also caused a significant downregulation in MxA expression in Imiquimod-stimulated PBMCs (*P = 0.0218). In conclusion, TAM displays several paradoxical effects in PBMCs of males infected with HCV compared to those of females. Contrary to the previous study involving premenopausal females, in PBMCs of infected males TAM may decrease IFNα release as indicated by reduced MxA expression possibly via the suppression of TLR7 expression.
authors.affiliation: The Molecular Pathology Research Group, Department of Pharmacology, German University in Cairo, Cairo, Egypt.
authors.forename: Injie O
authors.initials: IO
authors.lastname: Fawzy
authors.forename: Mohamed
authors.initials: M
authors.lastname: Negm
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 I
authors.initials: AI
authors.lastname: Abdelaziz
mesh_terms: D002478:Cells, Cultured; D015536:Down-Regulation; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D020869:Gene Expression Profiling; D019698:Hepatitis C, Chronic / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology; D008297:Male; D064547:Myxovirus Resistance Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D060888:Real-Time Polymerase Chain Reaction; D013629:Tamoxifen / Q000494:pharmacology*; D051199:Toll-Like Receptor 7 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*
chemical_list: D004965:Estrogen Antagonists; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; C495348:TLR7 protein, human; D051199:Toll-Like Receptor 7; D013629:Tamoxifen
keywords: JAK-STAT pathway; gender; interferon alpha