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

Objective and Design: the aim of the study was to decipher the molecular signals involved in IL-1's action on intestinal epithelial cells (IEC). Materials and Methods: Mode-K cells, used as a model of IEC, were treated with IL-1, and PLA, activity and PGE, ceramide, and cyclooxygenase-2 (COX-2) levels were measured using enzyme-immuno-assay kit, EIA, thin-layer chromatography and western blotting assays respectively. Results: IL-1 caused a concentration- and time-dependent increase in PLA, activity (3-fold increase), in ceramide levels (peak increase = 10.5 +/- 0.9 pmol/nmol phosphate), and in COX-2 and PGE, levels. PGE(2) increase was biphasic with an early peak at 10 min (around 5 ng/mg protein) due to increased PLA(2) activity. The later peak (13.1 +/- 1.9 ng/mg protein) at 4 It was due to COX-2 induction. Conclusion: In conclusion, these findings demonstrate that IL-1 regulates IEC function through two pathways, the PLA(2) and the sphingomyelin pathways, both of which are capable of modulating the inflammatory process.