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

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Abstract

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.

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  • Organic Chemistry
Original languageEnglish
Pages (from-to)829-834
JournalBiological Chemistry
Volume385
Issue number9
Publication statusPublished - 2004
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Organic chemistry (S/LTH) (011001240)