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

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Author

Summary, in 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.

Publishing year

2004

Language

English

Pages

829-834

Publication/Series

Biological Chemistry

Volume

385

Issue

9

Document type

Journal article

Publisher

De Gruyter

Topic

  • Organic Chemistry

Status

Published

ISBN/ISSN/Other

  • ISSN: 1437-4315