TNF-a suppresses CTGF expression

Excerpt

Collagen deposition is an essential part of normal tissue development and wound healing; however, excessive accumulation of collagen is central to fibrotic disorders such as scleroderma. The pleiotropic cytokine TGF? is an essential cytokine in normal tissue development, necessary for fibroblast proliferation and induction of collagen deposition. Transiently elevated TGF? levels induce collagen deposition in normal wound healing, but TGF? continues to be expressed during uncontrolled fibrotic events. TGF? is essential for induction of CTGF production by fibroblasts, resulting in collagen deposition. CTGF is overexpressed in fibrotic disorders; therefore, understanding the factors that mediate its action may be important in understanding them. This paper investigated the ability of TNF-a to suppress TGF?-induced CTGF production in normal fibroblasts. TGF? induction and TNF-a suppression of CTGF expression by normal fibroblasts was found to act through the same promoter in the CTGF gene. In scleroderma patients CTGF was constitutively produced, was enhanced by TGF? and could not be ablated with TNF-a. To examine the role of TNF-a in suppressing TGF?-induced CTGF in fibroblasts. …