Regulation by transforming growth factor-beta1 of class II mRNA and protein expression in fibroblast-like synoviocytes from patients with rheumatoid arthritis.
Transforming growth factor (TGF)-beta1 is an immunosuppressive cytokine that modulates the expression of class II histocompatibility antigens on human cells. Aberrant HLA class II expression on synovial lining cells of rheumatoid arthritis synovial membrane has been described, and the extent and intensity of class II expression on the cells was claimed to be linked with the severity of the disease. In this study, the effects of TGF-beta1 on HLA class II antigen expression in fibroblast-like synoviocytes (SFC) from rheumatoid synovectomy tissues were determined by flow cytometric analysis and quantitative RT-PCR. We found that pre-incubation of cells with TGF-beta1 was able to down-regulate IFN-gamma-induced DR protein expression in SFC. TGF-beta1, additionally, down-regulated IFN-gamma-stimulated class II transactivator (CIITA) and DRB mRNA expression. The constitutive expression of CIITA mRNA was completely abolished and the constitutive expression of DRB mRNA was decreased after treatment of SFC with TGF-beta1 for 24 h. Addition of the TGF-beta inhibitor decorin to SFC for 24 h before TGF-beta1/IFN-gamma treatment was able to reduce the down-regulatory effect of TGF-beta1 on DR antigen expression induced by IFN-gamma. Using competitive RT-PCR, we found that SFC constitutively expressed decorin mRNA and that treatment of cells with TGF-beta1 for 24 h reduced the constitutive expression of decorin mRNA by 65%. Our results show that TGF-beta1 is able to reduce the expression of HLA class II mRNA and protein, and suggest a tight regulation between TGF-beta1 and decorin in SFC of the rheumatoid synovium.
Navarrete Santos
A
A
Institute of Medical Immunology, Martin Luther University Halle-Wittenberg, Halle, Germany.
Kehlen
A
A
Schütte
W
W
Langner
J
J
Riemann
D
D
D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology; D002478:Cells, Cultured; D058575:Decorin; D015536:Down-Regulation / Q000187:drug effects; D016326:Extracellular Matrix Proteins; D005786:Gene Expression Regulation / Q000187:drug effects; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D009687:Nuclear Proteins; D011509:Proteoglycans / Q000235:genetics / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins; D013583:Synovial Membrane / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D015534:Trans-Activators / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; D000949:Histocompatibility Antigens Class II; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D011509:Proteoglycans; D012333:RNA, Messenger; D011994:Recombinant Proteins; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma