Involvement of intracellular signaling in the IL-1ß inhibitory effect on fructose intestinal absorption.

ABSTRACT

A variety of bacteria and their excreted/secreted products having direct effects on epithelial ion transport and permeability and the release of cytokines during bacterial infection may impact directly on epithelial function. Interleukin-1ß (IL-1ß) is a pleiotropic cytokine that affects the intestinal absorption of nutrients. The aim of this work was to study the intracellular signaling pathways involved in the inhibitory effect of IL-1ß on D-fructose intestinal transport in rabbit jejunum and Caco-2 cells. The results show that the cytokine inhibitory effect was completely reversed in presence of proteasome or PKC selective inhibitors in IL-1ß treated rabbits. In addition, the activation of PI3K abolished the IL-1ß effect. Likewise, these results were confirmed in Caco-2 cells. In addition, p-PI3K expression was increased by IL-1ß-treatment whereas the expression of p-PKCα was not significantly affected. In summary, the results suggest that IL-1ß could regulate the activation of pPKCα 73, pPI3K 55, and NF-kB proteins. These events could exert an inhibitory effect on fructose intestinal absorption by a modification of GLUT5 insertion to brush-border membrane and/or the functional transporter activity. This effect is independent of hormonal milieu and nervous stimuli.