IL-1 activates two phospholipid signaling pathways in intestinal epithelial cells.

Abstract

the aim of the study was to decipher the molecular signals involved in IL-I's action on intestinal epithelial cells (IEC). Mode-K cells, used as a model of IEC, were treated with IL-I, and PLA2 activity and PGE2, ceramide, and cyclooxygenase-2 (COX-2) levels were measured using enzyme-immuno-assay kit, EIA, thin-layer chromatography and western blotting assays respectively. IL-I caused a concentration- and time-dependent increase in PLA2 activity (3-fold increase), in ceramide levels (peak increase = 10.5 +/- 0.9 pmol/nmol phosphate), and in COX-2 and PGE2 levels. PGE2 increase was biphasic with an early peak at 10 min (around 5 ng/mg protein) due to increased PLA2 activity. The later peak (13.1 +/- 1.9 ng/mg protein) at 4 h was due to COX-2 induction. In conclusion, these findings demonstrate that IL-I regulates IEC function through two pathways, the PLA2 and the sphingomyelin pathways, both of which are capable of modulating the inflammatory process.