High expression and autoinduction of monocyte chemoattractant protein-1 inscleroderma fibroblasts

Systemic sclerosis (SSc) is a connective tissue disease with unknown etiolo gy characterized by excessive deposition of extracellular matrix in the ski n as well as various internal organs. In the early stages of SSc, inflammat ory infiltrates of mononuclear cells are found in the dermis, which is asso ciated with increased collagen synthesis produced by activated fibroblasts. Monocyte chemoattractant protein-1 (MCP-1) is a predominant monocyte chemo attractant secreted by a variety of cell types, and recent in vivo and in v itro studies suggest the involvement of MCP-1 in tissue fibrosis. Here we d emonstrate that cultured scleroderma fibroblasts, compared to fibroblasts f rom 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 abroga ted by actinomycin D. These findings suggest that MCP-1 plays an important role in the induction of scleroderma by MCP-1 release from fibroblasts, whi ch results in recruitment of monocytes to the skin. Moreover, increased res ponsiveness of scleroderma fibroblasts to MCP-1 could result in a continuat ion of the fibrotic response.