Regulatory effect of extracellular signal-regulated kinases (ERK) on type I collagen synthesis in human dermal fibroblasts stimulated by IL-4 and IL-13.

Synthesis of collagen is up-regulated by pro-fibrogenic growth factors and cytokines such as TGF-beta 1, IL-4, and IL-13 binding to their corresponding cell membrane receptors of fibroblasts. The ERK pathway is an important MAPK signaling pathway that is involved in regulating cell function. The aim of our studies was to examine effects of IL-4 and IL-13 on the ERK signaling pathway and its function in regulating type I collagen gene expression in human fibroblasts.

Molecular aspects of regulation of collagen gene expression in fibrosis.

Fibrosis, the hyper-accumulation of scar tissue, is characterized by the overproduction and deposition of type I and III collagen by fibroblasts and is the one of the main pathologic outcomes of the autoimmune disorder scleroderma. While the causes of fibrosis in scleroderma are unknown, cytokines such as TGF-beta, IL-4 and IL-13, play a crucial role in the stimulation of collagen production have been implicated in the disease process. In fibroblasts stimulation of collagen production by these cytokines is dependent on the Smad and STAT6 signaling pathways induced by TGF-beta and IL-4, IL-13 respectively.

B cells: no longer bystanders in liver fibrosis.

Cytokines secreted by cells that mediate the innate and adaptive immune responses play a critical role in regulating the synthesis of ECM components by fibroblasts. Overexpression and deposition of ECM components are dominant features of fibrotic diseases, including hepatic fibrosis. The contribution of CD4+ Th2 cells to hepatic fibrosis has been well described.