Background: Urinary tract infection is a common occurrence often associated with renal interstitial inflammation in the form of accumulation of mononuclear cells. We hypothesized that bacteria activate tubular cells to secrete cytokines, which may promote migration of mononuclear cells at the site of interaction.
Materials and methods: We evaluated the migration of monocytes in response to tubular cell products (TC-S) and interaction products of E. coli with proximal tubular cells (TC-EC-S; concentrations of 5%, 10%, and 25%) using a modified Boyden chamber. To determine the molecular mechanism, we evaluated the effect of antibodies against macrophage-monocyte chemoattractant protein-1 (MCP-1) and transforming growth factor-beta (TGF-beta) on E. coli-tubular cell interaction product-induced migration of monocytes. In addition, we studied the effect of free-radical scavengers on activation of tubular cells.
Results: The TC-EC-S enhanced (p < 0.0001) migration of monocytes compared with TC-S. Both anti-TGF-beta and anti-MCP-1 antibodies partly inhibited (p < 0.0001) TC-EC-S-induced monocyte migration. The modified TC-EC-S (produced in the presence of superoxide dismutase [SOD], dimethyl thiourea [DMTU], or catalase, all scavengers of free radicals) induced lesser monocyte migration than did TC-EC-S alone.
Conclusions: These results suggest that E. coli activates tubular cells to generate cytokines such as MCP-1 and TGF-beta that promote migration of monocytes. Free radicals such as superoxide and hydrogen peroxide may be acting as second messengers in E. coli-induced tubular cell activation.