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Inhibition of inducible TNF-alpha expression by oxaspirodion, a novel spiro-compound from the ascomycete Chaetomium subspirale

Author:
  • J Rether
  • G Erkel
  • T Anke
  • Olov Sterner
Publishing year: 2004
Language: English
Pages: 829-834
Publication/Series: Biological Chemistry
Volume: 385
Issue: 9
Document type: Journal article
Publisher: De Gruyter

Abstract english

In a search for compounds inhibiting the inducible TNF-alpha promoter activity in T cells, a new spirocompound, designated oxaspirodion, was isolated from fermentations of the ascomycete Chaetomium subspirale. Oxaspirodion inhibited TNF-alpha promoterdriven luciferase reporter gene expression with an IC50 value of 2.5 mug/ml (10 muM) in TPA/ionomycinstimulated Jurkat T cells. Studies on the mode of action of the compound revealed that the inhibition of the TNF-alpha promoter activity is caused by an inhibition of the phosphorylation of the ERK1/2 kinases. In addition, oxaspirodion inhibited the activation of the transcription factor NF-kappaB, which is involved in the inducible expression of many proinflammatory genes.

Keywords

  • Organic Chemistry

Other

Published
  • ISSN: 1437-4315
Olov Sterner
E-mail: olov.sterner [at] science.lu.se

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