TGF-beta and TNF-alpha: antagonistic cytokines controlling type I collagen gene expression.

The balance between production and degradation of type I collagen plays a critical role in the development and maintenance of organ and tissue integrity. It also represents the most crucial element governing the process of tissue repair. The synthesis of type I collagen gene is highly regulated by different cytokines at the transcriptional level. Especially, transforming growth factor beta (TGF-beta), a key player in the physiopathology of tissue repair, enhances type I collagen gene expression. In contrast, tumor necrosis factor alpha (TNF-alpha), whose matrix-remodelling function is opposite to that of TGF-beta, reduces type I collagen gene expression. This review focuses on transcriptional regulation of type I collagen by TGF-beta and TNF-alpha and on the molecular mechanisms that control the antagonistic activity of TNF-alpha against TGF-beta-driven type I collagen gene expression.