Analysis of proteins that interact with the IL-2 regulatory region in patients with rheumatic diseases.
In order to investigate transcriptional regulation of lymphokine genes in rheumatic diseases, peripheral blood mononuclear cells from patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and systemic sclerosis (SSc) were analysed for expression of DNA-binding proteins. Nuclear extracts prepared from unstimulated and mitogen-activated cells were studied for their ability to bind to 32P-labelled oligonucleotides containing the AP-1, NF-AT, NF-B and CD28RC sites of the IL-2 promoter. Using gel mobility-shift assay, detection of protein binding to the AP-1 site was reduced in SLE compared with controls. NF-AT binding activity was enhanced in all groups of patients, and was associated with measures of disease activity in RA. In addition, SSc patients showed increased NF-kappa B binding activity. Altered patterns of DNA-binding proteins suggest disturbed intracellular signalling which may contribute to abnormal lymphokine production in rheumatic diseases.
Becker
H
H
III Medizinische Klinik und Poliklinik, Justus-Liebig-Universität Giessen, Germany.
Stengl
G
G
Stein
M
M
Federlin
K
K
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000276:immunology; D001483:Base Sequence; D018106:CD28 Antigens / Q000378:metabolism; D003240:Connective Tissue Diseases / Q000276:immunology*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000737:chemistry; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic / Q000502:physiology; D011485:Protein Binding; D012595:Scleroderma, Systemic / Q000276:immunology; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
D018106:CD28 Antigens; D004268:DNA-Binding Proteins; D007376:Interleukin-2; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D018808:Transcription Factor AP-1; D014157:Transcription Factors