COX-1 and COX-2 contribute differentially to the LPS-induced release of PGE2 and TxA2 in liver macrophages.
LPS induces an immediate release of thromboxane TxA2 and a delayed release of PGE2. Dexamethasone suppresses the LPS-induced release of TxA2 and PGE2. In the first 8 h after LPS addition, the specific COX-2 inhibitor SC236 inhibits the PGE2 and TxA2 release by about 80% and 20%, whereas the release of PGE2 and TxA2 between 8 and 24 h is inhibited by about 40% and 35%, respectively. Resident liver macrophages express substantial amounts of COX-1, TxAS, cPGES and mPGES-2, small amounts of COX-2 but almost no detectable amounts of mPGES-1. LPS induces an increase of COX-2 and mPGES-1, but does not change COX-1, cPGES, mPGES-2 and TxAS at protein level. Dexamethasone suppresses almost completely the LPS-induced effects on COX-2 and mPGES-1. It is concluded that (1) COX-1 and COX-2 are involved in the LPS-induced synthesis of TxA2 and PGE2; (2) TxA2 release is catalyzed at early time-points by the combined action of COX-1 and TxAs, whereas at later time points the newly expressed COX-2 couples to TxAS and contributes to the TxA2 release; (3) PGE2 release within the first 8 h is predominantly catalyzed by COX-2, whereas at later time-points COX-1 couples to the newly expressed mPGES-1 and contributes to the PGE2 release.
Bezugla
Yevgeniya
Y
Institute of Physiological Chemistry, Faculty of Medicine Carl Gustav Carus, Technical University Dresden, Fetscherstrasse 74, D-01307 Dresden, Germany.
Kolada
Angelika
A
Kamionka
Sabine
S
Bernard
Brigitte
B
Scheibe
Roland
R
Dieter
Peter
P
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002478:Cells, Cultured; D051545:Cyclooxygenase 1 / Q000096:biosynthesis*; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007728:Kupffer Cells / Q000166:cytology / Q000201:enzymology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000201:enzymology; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis*; D051381:Rats; D013928:Thromboxane A2 / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D013928:Thromboxane A2; D003907:Dexamethasone; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496513:Ptgs1 protein, rat; D015232:Dinoprostone