Differential chemokine production by colonic epithelial cells is thought to contribute to the characteristic increased infiltration of selected population of leukocytes cells in inflammatory bowel disease. We have previously demonstrated that IL-13 enhances IL-1α-induced IL-8 secretion by the colonic epithelial cell line HT-29. We have now explored the C-C chemokine expression and modulation in this system. The combination of TNF-α and IFN-γ was the minimal stimulation required for regulated on activation, normal T cell expressed and secreted (RANTES) and monocyte chemoattractant protein (MCP-1) mRNA expression and secretion by HT-29 cells. The same stimulation induced a stronger IL-8 mRNA expression and secretion. Pretreatment with IL-13 or IL-4, reduced significantly the RANTES, and MCP-1, but not IL-8 mRNA expression and secretion. In contrast, IL-10 had no effect on either MCP-1, or RANTES, or IL-8 generation. Pretreatment of HT-29 cells with wortmannin suggested that the IL-13-induced inhibition of C-C chemokine expression is via activation of a wortmannin-sensitive phosphatidylinositol 3-kinase. These data demonstrate that colonic epithelial cell chemokine production can be differentially regulated by T cell-derived cytokines and suggest an interplay between epithelial cells and T lymphocytes potentially important in the intestinal inflammation.