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Abstract
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.
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Article info
Publication history
Accepted:
June 18,
1996
Received:
May 15,
1996
Identification
Copyright
© 1996 Published by Elsevier Inc.
