Dihydrotestosterone inhibits tumor necrosis factor alpha induced interleukin-1alpha mRNA expression in rheumatoid fibroblast-like synovial cells.
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.
Itoh
Yuka
Y
Department of Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan.
Hayashi
Hidetoshi
H
Xu
Jian
J
Takii
Takemasa
T
Miyazawa
Keiji
K
Ariga
Hiroyoshi
H
Akahoshi
Tohru
T
Waguri-Nagaya
Yuko
Y
Otsuka
Takanobu
T
Okamoto
Takashi
T
Onozaki
Kikuo
K
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*
D059002:Androgen Receptor Antagonists; D053582:Interleukin-1alpha; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D013196:Dihydrotestosterone; C014290:hydroxyflutamide; D005485:Flutamide; D008156:Luciferases