YERSINIA ENTEROCOLITICA-INDUCED INTERLEUKIN-8 SECRETION BY HUMAN INTESTINAL EPITHELIAL-CELLS DEPENDS ON CELL-DIFFERENTIATION

In response to bacterial entry epithelial cells up-regulate expression and secretion of various proinflammatory cytokines, including interle ukin-8 (IL-8). We studied Yersinia enterocolitica O:8-induced IL-8 sec retion by intestinal epithelial cells as a function of cell differenti ation, For this purpose, human T84 intestinal epithelial cells were gr own an permeable supports, which led to the formation of tight monolay ers of polarized intestinal epithelial cells. To analyze IL-8 secretio n as a function of cell differential-ion, T84 monolayers were infected from the epical or basolateral side at different stages of differenti ation. Both virulent (plasmid-carrying) and nonvirulent (plasmid-cured ) Y. enterocolitica strains invaded nondifferentiated T84 cells from t he apical side. Yersinia invasion into T84 cells was followed by secre tion of IL-8. After polarized differentiation of T84 cells Y. enteroco litica was no longer able to invade from the epical side of to induce LL-S secretion by T84 cells. However, Y. enterocolitica invaded and in duced IL-8 secretion by polarized T84 cells after infection from the b asolateral side. Basolateral invasion required the presence of the Yer sinia invasion locus, inv, suggesting beta(1) integrin-mediated cell i nvasion, After basolateral infection, Yersinia-induced IL-8 secretion was not strictly dependent on cell invasion. Thus, although the plasmi d-carrying Y. enterocolitica strain did not significantly invade T84 c ells, it induced significant IL-8 secretion. Taken together, these dat a show that Yersinia-triggered IL-8 secretion by intestinal epithelial cells depends on cell differentiation and might be induced by invasio n as well as by basolateral adhesion, suggesting that invasion is not essential for triggering IL-8 production. Whether IL-8 secretion is in volved in the pathogenesis of Yersinia-induced abscess formation in Pe yer's patch tissue remains to be shown.