Escherichia coli-human uroepithelial cell interaction products enhance fibroblast migration and matrix accumulation

Background and Purpose: Urinary tract infection has been associated with re nal interstitial scarring and ureteral wall fibrosis. The mechanism of prog ression of scarring despite attenuation of the primary insult is not clear. We examined the role of the products of the interaction between Escherichi a coli and human uroepithelial cells (HUC-EC-S) on the migration of fibrobl asts, as well as their matrix synthesis. Materials and Methods: We evaluated the effect of HUC-EC-S (concentration o f 10%, 15%, and 25%) on the migration of fibroblasts across a filter in a m odified Boyden chamber. To determine the role of transforming growth factor -beta and MCP-1, we studied the effect of anti-TGF-beta and anti-MCP-1 anti bodies on interaction product-induced fibroblast migration. The effect of H UC-EC-S on fibronectin and collagen I accumulation was studied by the Weste rn blotting. Results: Bacterial-HUC interaction products enhanced (P < 0.001) migration of fibroblasts compared with uroepithelial interaction product (HUC-S). Ant i-TGF-<beta> and anti-MCP-1 antibodies partly inhibited (P < 0.001) the HUC -EC-S-induced fibroblast migration. Also, HUC-EC-S-treated fibroblasts show ed enhanced accumulation of fibronectin and collagen 1. Conclusion: Escherichia coli-induced activation of HUC not only promotes mi gration of fibroblasts but also triggers matrix remodeling.