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https://hdl.handle.net/2440/8981
Type: | Journal article |
Title: | Inhibition of prostaglandin endoperoxide synthase-2 expression in stimulated human monocytes by inhibitors of p38 mitogen-activated protein kinase |
Author: | Pouliot, M. Baillargeon, J. Lee, J. Cleland, L. James, M. |
Citation: | Journal of Immunology, 1997; 158(10):4930-4937 |
Publisher: | AMER ASSOC IMMUNOLOGISTS |
Issue Date: | 1997 |
ISSN: | 0022-1767 1550-6606 |
Statement of Responsibility: | Marc Pouliot, Josée Baillargeon, John C. Lee, Leslie G. Cleland, and Michael J. James |
Abstract: | Prostaglandin endoperoxide synthase (PGHS; cyclooxygenase), the rate-limiting enzyme in the conversion of arachidonic acid to prostanoids, has two isoforms. PGHS-1 is constitutively expressed and involved in homeostasis, whereas PGHS-2 is inducible in monocytes in response to proinflammatory agents. Using freshly elutriated human monocytes, we examined the effect on PGHS-2 expression of certain cytokine-suppressive anti-inflammatory drugs such as SK&F 86002. Incubation with serum-treated zymosan (STZ) stimulated the expression of PGHS-2 in a time- and dose-dependent manner. SK&F 86002 dose-dependently inhibited this STZ-induced expression of PGHS-2 protein, which correlated with a decrease in prostaglandin E2 and thromboxane A2 production. However, suppression of PGHS-2 expression is not the result of suppressed cytokine production, because SK&F 86002 suppressed PGHS-2 expression initiated by IL-1beta and TNF-alpha, in addition to other stimuli. Moreover, this effect was selective in that the protein expression of two other important enzymes involved in the metabolism of arachidonic acid, cytosolic phospholipase A2 and 5-lipoxygenase, was not affected. Stimulation with STZ caused a time-dependent increase in levels of PGHS-2 mRNA; incubation with cytokine-suppressive agents caused a decrease of these levels, suggesting the involvement of transcription and/or mRNA stability events in the inhibition of PGHS-2. These results indicate a new and potentially important anti-inflammatory property of SK&F 86002, namely the specific suppression of PGHS-2 induction. |
Keywords: | Monocytes Cells, Cultured Humans Imidazoles Pyridines Thiazoles Phospholipases A Arachidonate 5-Lipoxygenase Mitogen-Activated Protein Kinases p38 Mitogen-Activated Protein Kinases RNA, Messenger Interleukin-1 Enzyme Inhibitors Cyclooxygenase Inhibitors Gene Expression Regulation, Enzymologic Calcium-Calmodulin-Dependent Protein Kinases Phospholipases A2 |
Rights: | Copyright © 1997 by American Association of Immunologists |
Appears in Collections: | Aurora harvest 4 Medicine publications |
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