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Interferon γ induces differential upregulation of α and β chemokine secretion in colonic epithelial cell lines |
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| Authors: | A Warhurst S Hopkins G Warhurst |
| Abstract: | Background—Production of chemoattractant factorsby the intestinal epithelium may contribute to mucosal infiltration byinflammatory cells in inflammatory bowel disease. Secretion of the α chemokine interleukin 8 (IL-8), a neutrophil chemoattractant, has beenwidely studied, but little is known about epithelial secretion of β chemokines, which are preferentially involved in recruiting monocytes. Aims—To investigate the profiles of α and β chemokine secretion in colonic cell lines and their differentialmodulation by interferon γ (IFN-γ), a product of activated Tlymphocytes and natural killer cells. Methods and results—HT29-19A, a model of theCl secretory crypt cell, exhibited a parallel secretionof the α chemokines IL-8 and GROα, which could be markedlyupregulated by tumour necrosis factor α (TNF-α) and IL-1β. Thesecells showed no significant expression of the β chemokines RANTES(regulated upon activation T cell expressed and secreted), MIP-1α(macrophage inflammatory protein 1α), and MCP-1 (monocyte chemotacticprotein 1) under these conditions, but IFN-γ in combination withTNF-α caused a dose dependent induction of RANTES and MCP-1secretion. This was accompanied by a marked increase of RANTES mRNA. Incontrast, IFN-γ had no significant effect on TNF-α stimulated IL-8secretion. Caco-2 cells, with features more typical of villusabsorptive cells, were relatively poor secretors of α chemokines butsecreted high levels of MCP-1 in response to IL-1β. IFN-γ did notinfluence α or β chemokine secretion in these cells. Conclusions—These studies suggest that intestinalepithelial cells may produce chemokines capable of attracting bothneutrophils and monocytes. The ability of IFN-γ to activate theexpression of β chemokines preferentially could facilitate thedevelopment of chronic inflammatory infiltrates. Keywords:inflammatory bowel disease; RANTES; interferongamma; chemokine |
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