期刊
JOURNAL OF ANTIBIOTICS
卷 56, 期 4, 页码 337-343出版社
JAPAN ANTIBIOT RES ASSN
DOI: 10.7164/antibiotics.56.337
关键词
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In a search for new inhibitors of the IFN-gamma mediated signal transduction in HeLa S3 cells using secreted alkaline phosphatase (SEAP) as reporter gene, a novel compound, designated as S14-95 was isolated from fermentations of the imperfect fungus Penicillium sp. 14-95. The compound inhibits the IFN-gamma mediated expression of the reporter gene with IC50 values of 2.5similar to5 mug/ml (5.4similar to10.8 muM). Furthermore the compound inhibited the expression of the proinflammatory enzymes COX-2 and NOS II at 5 mug/ml (10.8 muM), in LPS/IFN-gamma stimulated J774 mouse macrophages. Studies on the mode of action of the compound revealed that the inhibition of the IFN-gamma dependent signaling pathway is, caused by an inhibition of the phosphorylation of the STAT1alpha transcription factor. In addition, S14-95 inhibited the activation of the p38 MAP kinase, which is involved in the inducible expression of many proinflammatory genes.
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