title: Dihydrotestosterone inhibits tumor necrosis factor alpha induced interleukin-1alpha mRNA expression in rheumatoid fibroblast-like synovial cells.
abstract: Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects multiple synovial joints. Proinflammatory cytokines, such as interleukin-1 (IL-1) and tumor necrosis factor (TNF)alpha play important roles as principle inflammatory and destructive components of the disease. RA is known to be associated with significant gender differences in its prevalence and clinical features. We found that a potent androgen, 5alpha-dihydrotestosterone (DHT) inhibits IL-1alpha mRNA expression induced by TNFalpha and the DHT effect was inhibited by an androgen receptor antagonist, hydroxyflutamide (OHF). DHT inhibited the NF-kappaB activation induced by TNFalpha in a manner dependent on the androgen receptor (AR). These results suggest that DHT inhibits the TNFalpha-induced IL-1alpha mRNA expression by inhibiting NF-kappaB activation, and contributes to the gender differences of the disease.
authors.affiliation: Department of Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Itoh
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Hayashi
authors.forename: Jian
authors.initials: J
authors.lastname: Xu
authors.forename: Takemasa
authors.initials: T
authors.lastname: Takii
authors.forename: Keiji
authors.initials: K
authors.lastname: Miyazawa
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Ariga
authors.forename: Tohru
authors.initials: T
authors.lastname: Akahoshi
authors.forename: Yuko
authors.initials: Y
authors.lastname: Waguri-Nagaya
authors.forename: Takanobu
authors.initials: T
authors.lastname: Otsuka
authors.forename: Takashi
authors.initials: T
authors.lastname: Okamoto
authors.forename: Kikuo
authors.initials: K
authors.lastname: Onozaki
mesh_terms: D059002:Androgen Receptor Antagonists; D001172:Arthritis, Rheumatoid / Q000473:pathology; D018929:Cell Culture Techniques; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D013196:Dihydrotestosterone / Q000494:pharmacology*; D005485:Flutamide / Q000031:analogs & derivatives / Q000494:pharmacology; D017930:Genes, Reporter; D006801:Humans; D053582:Interleukin-1alpha / Q000037:antagonists & inhibitors*; D008156:Luciferases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013583:Synovial Membrane / Q000166:cytology*; D013997:Time Factors; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D059002:Androgen Receptor Antagonists; D053582:Interleukin-1alpha; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D013196:Dihydrotestosterone; C014290:hydroxyflutamide; D005485:Flutamide; D008156:Luciferases