Effects of non-steroidal anti-inflammatory drugs on prostaglandin E2 production by cyclooxygenase-2 from endogenous and exogenous arachidonic acid in rat peritoneal macrophages stimulated with lipopolysaccharide.
Lipopolysaccharide (LPS) stimulated prostaglandin E2 (PGE2) formation and induction of cyclooxygenase-2 (COX-2) expression without changing the levels of COX-1 protein in rat peritoneal macrophages. Non-steroidal anti-inflammatory drugs (NSAIDs) (nimesulide, indomethacin and ibuprofen) strongly inhibited LPS-stimulated PGE2 production without any effect on COX-2 protein expression, suggesting that NSAIDs are active in inhibiting the ability of COX-2 to convert arachidonic acid (AA) endogenously released in response to LPS stimulation. Exogenous AA can be converted to PGE2 by both COX isoforms even in LPS-stimulated macrophages. NSAIDs inhibited PGE2 production from exogenous AA mediated by both COX-1 and COX-2. However, the two isoforms interacted differentially with different NSAIDs. Furthermore, NSAIDs were distinctly more active in inhibiting PGE2 production from endogenous AA than that from exogenous AA. These data suggest that PGE2 production through COX-2 from exogenous AA may not be subject to the same regulatory processes as that from endogenous AA and the two metabolic processes may be differentially sensitive to different NSAIDs.
Nakatsugi
S
S
Osaka Research Laboratory, Sawai Pharmaceutical Co. Ltd., Japan.
Sugimoto
N
N
Furukawa
M
M
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000378:metabolism* / Q000494:pharmacology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis*; D007052:Ibuprofen / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007527:Isoenzymes / Q000187:drug effects / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D013449:Sulfonamides; D016718:Arachidonic Acid; D003907:Dexamethasone; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; D015232:Dinoprostone; C012655:nimesulide; D007052:Ibuprofen; D007213:Indomethacin