Monocyte chemoattractant protein-1 mediates collagen deposition in experimental glomerulonephritis by transforming growth factor-beta

Background. Monocyte chemoattractant protein-1 (MCP-1) plays a significant role in the recruitment of monocytes/macrophages in experimental glomerulon ephritis (GN). Because recent evidence points to possible profibrogenic eff ects of leukocyte-derived factors in GN, this study was designed to evaluat e the role of the chemokine MCP-1 in the fibrogenesis of experimental GN. Methods. Rats with an anti-thy-1-induced GN were treated with a neutralizin g antiserum against MCP-1. Glomerular collagen type IV, as a marker of glom erular matrix deposition, was assessed by Northern and Western blotting and immunohistology. Transforming growth factor-beta (TGF-beta), an important mediator of this matrix expansion, was studied by Northern and Western blot ting. Results. The induction of GN resulted in a significant increase of glomerul ar collagen type IV deposition and TGF-beta synthesis. The neutralization o f MCP-1 significantly reduced the enhanced collagen type IV protein synthes is and deposition without affecting collagen mRNA expression. However, both the enhanced transcription and protein synthesis of TGF-beta were inhibite d by anti-MCP-1 antiserum in nephritic animals. Conclusions. In this model of GN, MCP-1 has a fibrogenic effect through the stimulation of TGF-beta. MCP-1 is thus not only important for the recruitm ent of inflammatory cells, but also mediates glomerular matrix accumulation .