Inhibition of tumor necrosis factor-alpha production by SK&F 98625, a CoA-independent transacylase inhibitor, in cultured rat peritoneal macrophages.
When rat peritoneal macrophages were incubated in medium containing thapsigargin, tumor necrosis factor-alpha (TNF-alpha) production was increased time-dependently. In the presence of SK&F 98625, a CoA-independent transacylase inhibitor, the thapsigargin-induced TNF-alpha production was inhibited dose-dependently. Platelet-activating factor (PAF) and prostaglandin E2 (PGE2) production were also inhibited by SK&F 98625. The SK&F 98625-induced inhibition of TNF-alpha production was not prevented by addition of PGE2. PAF antagonists such as E6123, L-652,731 and CV-6209 partially inhibited the thapsigargin-induced TNF-alpha production, suggesting that concurrently produced PAF in thapsigargin-stimulated macrophages up-regulates TNF-alpha production. The inhibition by SK&F 98625 of thapsigargin-induced TNF-alpha production might be partly due to the inhibition of PAF production.
Yamada
M
M
Department of Pathophysiological Biochemistry, Faculty of Pharmaceutical Sciences, Tohoku University, Sendai, Miyagi, Japan.
Ichinowatari
G
G
Tanimoto
A
A
Yaginuma
H
H
Ohuchi
K
K
D000217:Acyltransferases / Q000037:antagonists & inhibitors*; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005663:Furans / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011726:Pyridinium Compounds / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013047:Specific Pathogen-Free Organisms; D019284:Thapsigargin / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism
D001381:Azepines; D004791:Enzyme Inhibitors; D005663:Furans; D007093:Imidazoles; D009943:Organophosphorus Compounds; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D011726:Pyridinium Compounds; C093303:SK&F 98625; D014230:Triazoles; D014409:Tumor Necrosis Factor-alpha; C053321:CV 6209; C068033:E 6123; D019284:Thapsigargin; C047504:2,5-bis(3,4,5-trimethoxyphenyl)tetrahydrofuran; D000217:Acyltransferases; C039766:arachidonyl transacylase; D015232:Dinoprostone