A DISTINCT ARRAY OF PROINFLAMMATORY CYTOKINES IS EXPRESSED IN HUMAN COLON EPITHELIAL-CELLS IN RESPONSE TO BACTERIAL INVASION

Pathogenic bacteria that penetrate the intestinal epithelial barrier s timulate an inflammatory response in the adjacent intestinal mucosa. T he present studies asked whether colon epithelial cells can provide si gnals that are important for the initiation and amplification of an ac ute mucosal inflammatory response. Infection of monolayers of human co lon epithelial cell lines (T84, HT29, Caco-2) with invasive strains of bacteria (Salmonella dublin, Shigella dysenteriae, Yersinia enterocol itica, Listeria monocytogenes, enteroinvasive Escherichia coli) result ed in the coordinate expression and upregulation of a specific array o f four proinflammatory cytokines, IL-8, monocyte chemotactic protein-1 , GM-CSF, and TNF alpha, as assessed by mRNA levels and cytokine secre tion. Expression of the same cytokines was upregulated after TNF alpha or IL-1 stimulation of these cells. In contrast, cytokine gene expres sion was not altered after infection of colon epithelial cells with no ninvasive bacteria or the noninvasive protozoan parasite, G. lamblia. Notably, none of the cell lines expressed mRNA for IL-2, IL-4, IL-5, I L-6, IL-12p40, IFN-gamma, or significant levels of IL-1 or IL-10 in re sponse to the identical stimuli. The coordinate expression of IL-8, MC P-1, GM-CSF and TNF alpha appears to be a general property of human co lon epithelial cells since an identical array of cytokines, as well as IL-6, also was expressed by freshly isolated human colon epithelial c ells. Since the cytokines expressed in response to bacterial invasion or other proinflammatory agonists have a well documented role in chemo taxis and activation of inflammatory cells, colon epithelial cells app ear to be programmed to provide a set of signals for the activation of the mucosal inflammatory response in the earliest phases after microb ial invasion.