Regulation of interleukin-1beta-induced interleukin-6 gene expression in human fibroblast-like synoviocytes by glucocorticoids.
Involvement of interleukin-6 (IL-6) in the pathogenesis of rheumatoid arthritis (RA) has recently been demonstrated. In the present study, the regulation of IL-6 gene expression by glucocorticoids and IL-1beta in fibroblast-like synoviocytes (FLSs) was investigated. Both synthetic and natural glucocorticoids, i.e., dexamethasone (DEX) and hydrocortisone (HC), respectively, concentration-dependently inhibited protein production and gene expression of IL-6 by human FLSs. The effect of DEX was dependent on de novo protein synthesis. DEX significantly reduced the rate of IL-6 gene transcription without affecting the stability of IL-6 mRNA. The IkappaBalpha pathway seemed not to be involved in DEX-mediated inhibition of IL-6 gene expression in IL-1beta-stimulated human FLSs. These findings suggest that glucocorticoids suppress IL-6 gene transcription by an as yet undefined mechanism.
Miyazawa
K
K
Planning, Discovery Research, R&D, Kissei Pharmaceutical Co., Ltd., Hotaka Minamiazumi, Nagano, 399-8304, Japan.
Mori
A
A
Okudaira
H
H
D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D005347:Fibroblasts; D015870:Gene Expression / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D020672:I-kappa B Proteins; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology*; D015850:Interleukin-6 / Q000235:genetics*; D000072000:NF-KappaB Inhibitor alpha; D009687:Nuclear Proteins / Q000187:drug effects / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects; D013582:Synovial Fluid; D013583:Synovial Membrane / Q000166:cytology* / Q000187:drug effects; D014157:Transcription Factors / Q000187:drug effects / Q000378:metabolism; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D005938:Glucocorticoids; D020672:I-kappa B Proteins; D007375:Interleukin-1; D015850:Interleukin-6; C000606204:NFKBIA protein, human; D009687:Nuclear Proteins; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D014157:Transcription Factors; D000072000:NF-KappaB Inhibitor alpha; D003907:Dexamethasone; D003513:Cycloheximide