C-X-C and C-C chemokine expression and secretion by the human colonic epithelial cell line, HT-29: differential effect of T lymphocyte-derived cytokines

Differential chemokine production by colonic epithelial cells is thought to contribute to the characteristic increased infiltration of selected popula tion of leukocytes cells in inflammatory bowel disease. We have previously demonstrated that IL-13 enhances IL-1 alpha-induced IL-8 secretion by the c olonic epithelial cell line HT-29. We have now explored the C-C chemokine e xpression and modulation in this system. The combination of TNF-alpha and I FN-gamma 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 stim ulation 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 I L-8 mRNA expression and secretion. In contrast, IL-10 had no effect on eith er MCP-I, or RANTES, or IL-8 generation. Pretreatment of HT-29 cells with w ortmannin suggested that the IL-13-induced inhibition of C-C chemokine expr ession is via activation of a wortmannin-sensitive phosphatidylinositol 3-k inase. These data demonstrate that colonic epithelial cell chemokine produc tion can be differentially regulated by T cell-derived cytokines and sugges t an interplay between epithelial cells and T lymphocytes potentially impor tant in the intestinal inflammation.