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An inhibitor of thromboxane production attenuates tumor necrosis factor release by activated human alveolar macrophages.

Authors
Kuhn DC; Stauffer JL; Gaydos LJ
Source
CA Selects: Prostaglandins 1993 Sep; 46(3):195-205
NIOSHTIC No.
10004862
Abstract
Tumor necrosis factor alpha (TNF?) and thromboxane A2 (TXA2) are major products of the activated alveolar macrophage and serve as key mediators of lung injury. In order to determine if the synthesis of TXA2 and the release of TNF? are associated, the production of these inflammatory agents by the human alveolar macrophage (AM), as a result of activation by lipopolysaccharide (LPS), was assessed in the absence and presence of the thromboxane synthase inhibitors UK 38,485 (Dazmegrel) and OKY 046. UK 38,485 and OKY 046 inhibited both LPS-stimulated TXA2 production and TNF? release in a dose-dependent manner. Prostaglandin E2 (PGE2) production was not increased by UK 38,485 or OKY 046. Neither LPS nor UK 38,485 had any effect on LTB4 production by AM. Neither UK 38,485 or OKY 046 had any effect on LPS-stimulated interleukin-1 beta release. However, the TXA2 mimetic, U46619, did not stimulate TNF? release by AM either in the absence or presence of UK 38,485. These findings suggest that 1) UK 38,485 and OKY 046 are inhibitors of both TXA2 production and TNF? release by activated human AM, 2) UK 38,485 probably does not exert its inhibitory action on TNF? release through effects on eicosanoid production and 3) the possibility that TNF?- and TXA2-induced lung injury may be subject to amelioration by imidazole-based compounds should be further evaluated.
CODEN
CSEPDE
Publication Date
19930901
Document Type
Journal Article
Fiscal Year
1993
Identifying No.
MIR 10-94
Issue of Publication
3
ISSN
0148-2343
Source Name
CA Selects: Prostaglandins
State
CA
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