Phytic acid down-regulates IL-8 secretion from colonic epithelial cells by influencing mitogen-activated protein kinase signaling pathway.

Phytic acid (IP6) is an essential component of high fiber diet physiologically present in human large gut. It has been recognized to possess various significant health benefits effects including chemopreventive and have antineoplastic activity against various types of cancer. Moreover, its role in immune response through modulation of the secretion of proinflammatory cytokines and chemokines has been postulated. One of the sig- nal transduction pathways involved in a variety of inflammatory responses is p38 mitogen-activated protein kinase (MAPK) pathway. The aim of this study was to examine effect of IP6 on human p38α MAP kinase activ- ity and the expression of gene encoding p38 MAP kinase in unstimulated and IL-1β-stimulated Caco-2 cells. Furthermore, the role of signaling pathways involving p38 MAP kinase in IP6-induced down-regulation of IL- 8 secretion by unstimulated and IL-1β-stimulated cells in the presence of p38 MAP kinase activator (ani- somycin) and inhibitor (SB 203580) was evaluated. IP6 inhibited activity of recombinant p38 MAPK activity in dose-dependent manner. Treatment of cells with IP6 for 3 h resulted in decreased p38 MAP kinase expres- sion in both unstimulated and stimulated with IL-1β cells. The similar level of p38α mRNA was found in untreated and treated with IP6 cells after 6 and 12 h. Incubation of Caco-2 cells with anisomycin resulted in up- regulation of IL-8 secretion and their pretreatment with anisomycin prior to IP6 addition showed down-regula- tion of IL-8 secretion compared to cells treated with anisomycin alone. The findings of this study show that p38 MAPK could be one of the molecular targets for IP6 in the intestinal epithelial cells and that IP6 inhibitory effect on IL-8 secretion by Caco-2 cells could be mediated by its inhibition of p38 activity.