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Jan Rether, Gerhard Erkel, Timm Anke, Olov Sterner

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

Keywords: ERK, NF-?B, oxaspirodion, TNF-? synthesis

In a search for compounds inhibiting the inducible TNF-?a promoter activity in T cells, a new spiro-compound, designated oxaspirodion, was isolated from fermentations of the ascomycete Chaetomium subspirale. Oxaspirodion inhibited TNF-? promoter-driven luciferase reporter gene expression with an IC₅₀ value of 2.5 µg/ml (10 µM) in TPA/ionomycin-stimulated Jurkat T cells. Studies on the mode of action of the compound revealed that the inhibition of the TNF-? 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-?B, which is involved in the inducible expression of many proinflammatory genes.

Biological Chemistry, Walter de Gruyter

Print ISSN: 1431-6730
Volume: 385, 09/2004
Pages: 829 - 834

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