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Abstract

Platelet-activating factor production in stimulated macrophages is down-regulated by concurrently produced prostaglandin E2.

M Yamada, M Watanabe, S Mue and K Ohuchi
Journal of Pharmacology and Experimental Therapeutics June 1996, 277 (3) 1607-1614;
M Yamada
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M Watanabe
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S Mue
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K Ohuchi
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Abstract

When rat peritoneal macrophages were incubated in medium containing 12-O-tetradecanoylphorbol 13-acetate (TPA), a protein kinase C activator, production of cell-associated platelet-activating factor (PAF) and extracellular prostaglandin E2 (PGE2) increased. In the presence of the cyclooxygenase inhibitor indomethacin, TPA-induced PAF production was further enhanced dose-dependently in accordance with decrease of PGE2 levels. In addition, indomethacin further enhanced PAF production that was stimulated by the protein kinase C activators, aplysiatoxin and teleocidin. Other cyclooxygenase inhibitors such as naproxen and ibuprofen also enhanced TPA-stimulated PAF production in accordance with inhibition of PGE2 production. Cyclooxygenase inhibitor-induced enhancement of PAF production was markedly prevented by exogenous PGE2. Exogenous arachidonic acid also inhibited TPA-induced PAF production in parallel with increase in PGE2 levels. Inhibition of PAF production by exogenous arachidonic acid was abolished by indomethacin. Furthermore, PAF production stimulated by the endomembrane Ca+2-ATPase inhibitors thapsigargin or thapsigargicin, or by the Ca+2 ionophore A23187, was also enhanced by indomethacin in compensation for the decrease in PGE2 production. In addition, the adenylate cyclase activator forskolin, or the cyclic adenosine monophosphate (cAMP) analogues 8-bromo cAMP and dibutyryl cAMP inhibited thapsigargin-induced PAF production. TPA-induced accumulation of intracellular cAMP was inhibited by indomethacin, and indomethacin-induced decrease of cAMP level was reversed by exogenous PGE2. These results suggested that concurrently produced PGE2 in stimulated macrophages down-regulates PAF production via adenylate cyclase and cAMP pathway.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 277, Issue 3
1 Jun 1996
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Abstract

Platelet-activating factor production in stimulated macrophages is down-regulated by concurrently produced prostaglandin E2.

M Yamada, M Watanabe, S Mue and K Ohuchi
Journal of Pharmacology and Experimental Therapeutics June 1, 1996, 277 (3) 1607-1614;

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Abstract

Platelet-activating factor production in stimulated macrophages is down-regulated by concurrently produced prostaglandin E2.

M Yamada, M Watanabe, S Mue and K Ohuchi
Journal of Pharmacology and Experimental Therapeutics June 1, 1996, 277 (3) 1607-1614;
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