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

D. C. Kuhn, J. L. Stauffer, L. J. Gaydos, S. L. Lacey, L. M. Demers

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Tumor necrosis factor alpha (TNFα) 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 TNFα 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 TNFα 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 TNFα 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 TNFα release by activated human AM, 2) UK 38,485 probably does not exert its inhibitory action on TNFα release through effects on eicosanoid production and 3) the possibility that TNFα- and TXA2-induced lung injury may be subject to amelioration by imidazole-based compounds should be further evaluated.

Original languageEnglish (US)
Pages (from-to)195-205
Number of pages11
JournalProstaglandins
Volume46
Issue number3
DOIs
StatePublished - Sep 1993

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Endocrinology

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