Eicosanoid production by human monocytes: does COX-2 contribute to a self-limiting inflammatory response?
The eicosanoids, prostaglandin E2 (PGE2) and thromboxane A2 (TXA2), are involved in inflammatory events. TXA2 has potentially pro-inflammatory actions and PGE2 has actions which can be considered both pro- and antiinflammatory. Therefore, it is potentially significant that production of TXA2 and PGE2 by stimulated monocytes have very different time courses. TXA2 synthesis is immediate and dependent on cyclooxygenase Type 1 (COX-1) activity whereas PGE2 synthesis is delayed and dependent on COX-2 activity. These apparent COX-isotype dependencies of TXA2 and PGE2 synthesis can be explained by differences in the affinities of TXA synthase and PGE synthase for the common substrate, PGH2. The findings have implications for the use of NSAIDs and selective COX-2 inhibitors whose actions can increase the monocyte TXA2/PGE2 ratio.
James
M J
MJ
Rheumatology Unit, Royal Adelaide Hospital, Adelaide, SA, Australia. michael.james@adelaide.edu.au
Penglis
P S
PS
Caughey
G E
GE
Demasi
M
M
Cleland
L G
LG
D051546:Cyclooxygenase 2; D015777:Eicosanoids / Q000096:biosynthesis*; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism*; D008565:Membrane Proteins; D009000:Monocytes / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*
D015777:Eicosanoids; D007527:Isoenzymes; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases