IL-1 beta induces synthesis of phospholipase A2-activating protein in rabbit distal colon.
In inflammatory bowel disease, the colonic mucosa is infiltrated by inflammatory cells that secrete a variety of inflammatory mediators such as interleukin-1 beta (IL-1 beta). IL-1 beta caused a delayed increase in Cl- secretion and in prostaglandin E2 (PGE2) release in rabbit distal colon. Both of these effects were abolished with cycloheximide, implying a role for protein synthesis in mediating IL-1 beta's effect. With the use of Western blot assays, the protein was identified as the phospholipase A2 (PLA2)-activating protein (PLAP). IL-1 beta caused a concentration-dependent and a time-dependent increase in PLAP levels as well as in PLA2 activity, with the maximal increase observed at an IL-1 beta concentration between 10 and 30 ng/ml reached in 2-10 min. The PLAP mRNA levels were also regulated by IL-1 beta with a similar time course. PLAP is constitutively present in the epithelial cells and in the subepithelial layer of the distal colon. These findings suggest a direct effect of IL-1 beta on intestinal epithelial cells to cause an increase in PLAP levels and phospholipase A2 activity and subsequent increase in PGE2 levels.
Homaidan
F R
FR
Division of Gastroenterology, Winthrop-University Hospital, New York, USA.
Zhao
L
L
Burakoff
R
R
D000818:Animals; D002478:Cells, Cultured; D003106:Colon; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D004553:Electric Conductivity; D004789:Enzyme Activation; D007375:Interleukin-1 / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D014176:Protein Biosynthesis; D011506:Proteins; D012333:RNA, Messenger / Q000096:biosynthesis; D011817:Rabbits; D014158:Transcription, Genetic / Q000187:drug effects*
D007375:Interleukin-1; D011506:Proteins; D012333:RNA, Messenger; C055324:phospholipase A2-activating protein; D003609:Dactinomycin; D003513:Cycloheximide; D010741:Phospholipases A; D054467:Phospholipases A2; D015232:Dinoprostone