High expression and autoinduction of monocyte chemoattractant protein-1 in scleroderma fibroblasts

Systemic sclerosis (SSc) is a connective tissue disease with unknown etiology characterized by excessive deposition of extracellular matrix in the skin as well as various internal organs. In the early stages of SSc, inflammatory infiltrates of mononuclear cells are found in the dermis, which is associated with increased collagen synthesis produced by activated fibroblasts. Monocyte chemoattractant protein-1 (MCP-1) is a predominant monocyte chemoattractant secreted by a variety of cell types, and recent in vivo and in vitro studies suggest the involvement of MCP-1 in tissue fibrosis. Here we demonstrate that cultured scleroderma fibroblasts, compared to fibroblasts from control skin, spontaneously express significantly elevated MCP-1 levels. Interestingly, exogenously administered MCP-1 stimulated autoinduction of MCP-1 mRNA. This effect was specific to scleroderma fibroblasts and abrogated by actinomycin D. These findings suggest that MCP-1 plays an important role in the induction of scleroderma by MCP-1 release from fibroblasts, which results in recruitment of monocytes to the skin. Moreover, increased responsiveness of scleroderma fibroblasts to MCP-1 could result in a continuation of the fibrotic response.