Role of profibrogenic cytokines secreted by T cells in fibrotic processes in scleroderma.
IL-4 is potentially a major profibrogenic cytokine upregulating the expression of collagen genes. In vivo studies have shown that the disruption of STAT6, IL-4R, IL-4 or transforming growth factor-beta (TGF-beta) genes in TSK mice, which develop scleroderma-like syndrome, prevented the occurrence of skin sclerosis and of autoantibodies. Additionally, it is known that the homozygosity of TSK mutation is lethal and the embryos die by day 7-8 of pregnancy. The disruption of IL-4 gene rescued from death TSK/TSK mice suggesting a role for IL-4 in embryonic development. Since TGF-beta should compensate the lack of IL-4 on regulation of collagen gene expression, we have studied the effect of IL-4 on the expression of TGF-beta gene. Our results showed IL-4 dependence of the transcription of TGF-beta gene and that in both TSK/+ and TSK/TSK IL-4-/- mice the expression of TGF-beta gene is impaired.
McGaha
Tracy L
TL
Department of Microbiology, The Mount Sinai School of Medicine, Annenberg building 16-60, One Gustave L. Levy Place, New York, NY 10029, USA.
Bona
Constantin A
CA
D000818:Animals; D003094:Collagen / Q000276:immunology; D005355:Fibrosis / Q000276:immunology*; D006801:Humans; D015847:Interleukin-4 / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D012594:Scleroderma, Localized / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000276:immunology* / Q000378:metabolism
D016212:Transforming Growth Factor beta; D015847:Interleukin-4; D003094:Collagen