IL-1 activates two phospholipid signaling pathways in intestinal epithelial cells.
OBJECTIVE
the aim of the study was to decipher the molecular signals involved in IL-I's action on intestinal epithelial cells (IEC).


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Homaidan
F R
FR
American University of Beirut, Department of Physiology, New York, NY 10022, USA. fh01@aub.edu.lb
Chakroun
Dbaibo
G S
GS
El-Assaad
W
W
El-Sabban
M E
ME
D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D002518:Ceramides / Q000378:metabolism; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004847:Epithelial Cells / Q000187:drug effects*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007422:Intestines / Q000166:cytology / Q000187:drug effects; D007527:Isoenzymes / Q000096:biosynthesis; D008565:Membrane Proteins; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D010743:Phospholipids / Q000502:physiology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D011506:Proteins / Q000737:chemistry / Q000302:isolation & purification; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D013109:Sphingomyelins / Q000378:metabolism
D002518:Ceramides; D007375:Interleukin-1; D007527:Isoenzymes; D008565:Membrane Proteins; D010743:Phospholipids; D011506:Proteins; D011994:Recombinant Proteins; D013109:Sphingomyelins; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A; D054467:Phospholipases A2; D015232:Dinoprostone