Interferon ã induces diVerential upregulation of á and â chemokine secretion in colonic epithelial cell lines

Background—Production of chemoattractant factors by the intestinal epithelium may contribute to mucosal infiltration by inflammatory cells in inflammatory bowel disease. Secretion of the á chemokine interleukin 8 (IL-8), a neutrophil chemoattractant, has been widely studied, but little is known about epithelial secretion of â chemokines, which are preferentially involved in recruiting monocytes. Aims—To investigate the profiles of á and â chemokine secretion in colonic cell lines and their diVerential modulation by interferon ã (IFN-ã), a product of activated T lymphocytes and natural killer cells. Methods and results—HT29-19A, a model of the Cl secretory crypt cell, exhibited a parallel secretion of the á chemokines IL-8 and GROá, which could be markedly upregulated by tumour necrosis factor á (TNF-á) and IL-1â. These cells showed no significant expression of the â chemokines RANTES (regulated upon activation T cell expressed and secreted), MIP-1á (macrophage inflammatory protein 1á), and MCP-1 (monocyte chemotactic protein 1) under these conditions, but IFN-ã in combination with TNF-á caused a dose dependent induction of RANTES and MCP-1 secretion. This was accompanied by a marked increase of RANTES mRNA. In contrast, IFN-ã had no significant effect on TNF-á stimulated IL-8 secretion. Caco-2 cells, with features more typical of villus absorptive cells, were relatively poor secretors of á chemokines but secreted high levels of MCP-1 in response to IL-1â. IFN-ã did not influence á or â chemokine secretion in these cells. Conclusions—These studies suggest that intestinal epithelial cells may produce chemokines capable of attracting both neutrophils and monocytes. The ability of IFN-ã to activate the expression of â chemokines preferentially could facilitate the development of chronic inflammatory infiltrates. (Gut 1998;42:208–213)