Role of protein tyrosine kinase in the effect of IP6 on IL-8 secretion in intestinal epithelial cells.

Phytic acid (IP6) is a major fiber-associated component of a diet physiologically present in human intestines. Studies showed that this phytochemical can modulate immune functions of intestinal epithelium through regulation of proinflammatory cytokines secretion but mechanisms underlying these cellular response to IP6 have weakly been examined, as yet. The aim of this study was to determine the role of protein tyrosine kinase (PTK) in secretion of IL-8, a central proinflammatory cytokine, by unstimulated and IL-1beta-stimulated intestinal epithelial cells Caco-2 treated with IP6 (1 and 2.5 mM). To study the involvement of PTK signal pathway in IL-8 secretion, inhibitors of phosphotyrosine phosphatase (sodium orthovanadate, OV) and tyrosine kinase (genistein, GEN) were incubated with Caco-2 cells prior to IP6 treatment. IP6 had suppressive effect on basal and IL-1beta-stimulated IL-8 secretion by cells. The effect of OV on IL-8 release by cells treated with IP6 was different under constitutive and stimulated conditions. Secretion of IL-8 was significantly down-regulated in cells with GEN and GEN plus IP6 treatment. In addition, total PTK activity in both unstimulated and IL-1beta stimulated cells was determined in the presence of IP6. The results suggest that physiological intestinal concentrations of IP6 may have an inhibitory effect on IL-8 secretion by Caco-2 cells and one of the mechanisms of its action is the inhibition of PTK signaling cascade. The study revealed for the first time that PTKs could be one of the molecular targets for IP6 effects in the intestinal epithelial cells.