TNFalpha levels are increased during intestinal inflammation processes and malabsorption of nutrients may occur. We have previously demonstrated that TNFalpha inhibits galactose absorption in intestinal everted rings. The goal of the present work was to study the possible effect of TNFalpha on sugar absorption in Caco-2 cells. Before sugar flux and uptake measurements for 15 min, cells were preincubated for 1, 6 or 24 h with 10 ng/ml TNFalpha placed into the basal compartment. Alpha-methyl-D-glucoside, MG, (0.1 mM) was chosen as specific substrate of the Na⁺/glucose cotransporter SGLT1. In control conditions (absence of TNFalpha) sugar uptake was equal for all preincubation times (0.52 nmol/mg prot.) whereas flux increased with the preincubation period from 0.08 (1 h) to 0.18 nmol/cm2 (24 h). Transepithelial electrical resistance decreased with the preincubation time by 25 % after 1 h and by 45 % after 24 h, but it was not affected by TNFalpha. Following 1h preincubation, TNFalpha increased MG uptake by ~20 % and apical-basal flux by ~50 %. No change was observed after 6 h preincubation whereas after 24 h a decrease in the uptake (~15 %) and a high increase in flux was obtained. Preliminary experiments using 5 and 50 ng/ml TNFalpha for 1 h preincubation show no effect at 5 ng/ml and a decrease in MG uptake at 50 ng/ml. In summary, TNFalpha alters SGLT1 function in Caco-2 cells acting from the basolateral side.

This work was supported by PIUNA (University of Navarra).