Differential effects of 1,25-(OH)2D3 on acyl hydrolase and cyclooxygenase activities in interleukin 1 beta-stimulated human synovial fibroblast cultures.
Effects of proinflammatory cytokines on synovial fibroblasts are considered to play a role in the accumulation of prostaglandin E2 (PGE2) in the inflamed joint in rheumatoid arthritis. We have previously shown that interleukin 1 beta (IL-1 beta) induces PGE2 production in synovial fibroblast cultures and that this effect is suppressed by the active metabolite of vitamin D3, 1,25-(OH)2D3. To study the mechanism of the inhibitory action of 1,25-(OH)2D3, its effect on acyl hydrolase (arachidonic acid (AA) release) and cyclooxygenase (COX) activities were investigated. Our findings indicate that IL-1 beta caused an increase in AA release and COX activity and that in the presence of 1,25-(OH)2D3 AA release, but not COX activity, is suppressed. In comparison, dexamethasone, which also inhibits IL-1 beta induction of PGE2, had inhibitory effects on both parameters.
Meyer
F A
FA
Arthritis Research Unit, Ichilov Hospital, Tel Aviv-Sourasky Medical Center, Israel.
Yaron
I
I
Kamin-Belsky
N
N
Yaron
M
M
Raz
A
A
D016718:Arachidonic Acid / Q000378:metabolism*; D001172:Arthritis, Rheumatoid / Q000209:etiology; D002117:Calcitriol / Q000494:pharmacology*; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006801:Humans; D006867:Hydrolases / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects*
D007375:Interleukin-1; D016718:Arachidonic Acid; D011451:Prostaglandin-Endoperoxide Synthases; D006867:Hydrolases; D002117:Calcitriol; D015232:Dinoprostone