Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/8982
Type: Journal article
Title: Regulation of tumor necrosis factor-a and interleukin-1b synthesis by thromboxane A2 in nonadherent human monocytes.
Author: Caughey, G.
Pouliot, M.
Cleland, L.
James, M.
Citation: Journal of Immunology, 1997; 158(1):351-358
Publisher: AMER ASSOC IMMUNOLOGISTS
Issue Date: 1997
ISSN: 0022-1767
1550-6606
Statement of
Responsibility: 
G E Caughey, M Pouliot, L G Cleland and M J James
Abstract: Synthesis of TNF-alpha and IL-1beta, by monocytes/macrophages can be partially regulated by the eicosanoid, PGE2. We report here that inhibition of both PGE2 and thromboxane A2 (TXA2) synthesis by a prostaglandin H synthase inhibitor, NS-398, had no effect on the synthesis of either TNF-alpha or IL-1beta, even though the addition of PGE2 to these treated cells dose-dependently inhibited TNF-alpha and IL-1beta synthesis. Because TXA2 is a major eicosanoid product of stimulated human monocytes, we examined its influence on cytokine production. Inhibition of thromboxane synthase by carboxyheptyl imidazole (CI) resulted in inhibition of TNF-alpha (61 +/- 4.3%; n = 8; p < 0.001) and IL-1beta (54 +/- 4.2%; n = 8; p < 0.001) synthesis by serum-treated zymosan-stimulated nonadherent human monocytes. This effect was observed when cytokine production was measured by ELISA or bioactivity assays. Furthermore, the addition of a TXA2 agonist, carbocyclic TXA2, to CI-treated monocytes dose-dependently restored the levels of TNF-alpha and IL-1beta synthesis to those found with serum-treated zymosan stimulation alone. Inhibition of TXA2 activity by the thromboxane receptor antagonists, pinane TXA2 or SQ 29,548, also inhibited the production of TNF-alpha (67 +/- 2.4% and 65 +/- 2.7%, respectively; n = 8; p < 0.001) and IL-1beta (59 +/- 3.3% and 70 +/- 1.2%, respectively; n = 8; p < 0.001). Treatment with CI resulted in a partial decrease in TNF-alpha mRNA levels (60 +/- 12.0%; n = 4), but had little or no effect on IL-1beta mRNA levels. These novel observations implicate TXA2 as an important paracrine or autocrine facilitator of TNF-alpha and IL-1beta production in stimulated human monocytes and suggest that levels of TNF-alpha and IL-1beta synthesis are determined in part by the balance between TXA2 and PGE2 production in human monocytes.
Keywords: Monocytes; Cells, Cultured; Humans; Leukotriene B4; Dinoprostone; Thromboxane A2; Tumor Necrosis Factor-alpha; RNA, Messenger; Interleukin-1; Enzyme-Linked Immunosorbent Assay; Prostaglandin-Endoperoxide Synthases
RMID: 0030004860
Appears in Collections:Medicine publications

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