caa a22 4500 378884085 CHVBK 20180305123438.0 cr unu---uuuuu 161128e20040901xx s 000 0 eng 10.1515/BC.2004.108 doi (NATIONALLICENCE)gruyter-10.1515/BC.2004.108 Inhibition of inducible TNF-α expression by oxaspirodion, a novel spiro-compound from the ascomycete Chaetomium subspirale [Elektronische Daten] [Jan Rether, Gerhard Erkel, Timm Anke, Olov Sterner] In a search for compounds inhibiting the inducible TNF-αa promoter activity in T cells, a new spiro-compound, designated oxaspirodion, was isolated from fermentations of the ascomycete Chaetomium subspirale. Oxaspirodion inhibited TNF-α 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-α 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-κB, which is involved in the inducible expression of many proinflammatory genes. © Walter de Gruyter Biochemistry nationallicence Molecular biology nationallicence Cellular biology nationallicence ERK nationallicence NF-κB nationallicence oxaspirodion nationallicence TNF-α synthesis nationallicence Rether Jan Institut für Biotechnologie und Wirkstoff-Forschung e.V. (IBWF), Erwin-Schrödinger-Str. 56, D-67663 Kaiserslautern Germany aut Erkel Gerhard Institut für Biotechnologie und Wirkstoff-Forschung e.V. (IBWF), Erwin-Schrödinger-Str. 56, D-67663 Kaiserslautern Germany aut Anke Timm Institut für Biotechnologie und Wirkstoff-Forschung e.V. (IBWF), Erwin-Schrödinger-Str. 56, D-67663 Kaiserslautern Germany aut Sterner Olov Division of Organic Chemistry 2, Chemical Center, University of Lund, S-22100 Lund, Sweden aut Biological Chemistry Walter de Gruyter 385/9(2004-09-01), 829-834 1431-6730 385:9<829 2004 385 bchm https://doi.org/10.1515/BC.2004.108 text/html Onlinezugriff via DOI 1 research article jats NATIONALLICENCE 856 40 https://doi.org/10.1515/BC.2004.108 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Rether Jan Institut für Biotechnologie und Wirkstoff-Forschung e.V. (IBWF), Erwin-Schrödinger-Str. 56, D-67663 Kaiserslautern Germany aut NATIONALLICENCE 700 1- Erkel Gerhard Institut für Biotechnologie und Wirkstoff-Forschung e.V. (IBWF), Erwin-Schrödinger-Str. 56, D-67663 Kaiserslautern Germany aut NATIONALLICENCE 700 1- Anke Timm Institut für Biotechnologie und Wirkstoff-Forschung e.V. (IBWF), Erwin-Schrödinger-Str. 56, D-67663 Kaiserslautern Germany aut NATIONALLICENCE 700 1- Sterner Olov Division of Organic Chemistry 2, Chemical Center, University of Lund, S-22100 Lund, Sweden aut NATIONALLICENCE 773 0- Biological Chemistry Walter de Gruyter 385/9(2004-09-01), 829-834 1431-6730 385:9<829 2004 385 bchm CC0 http://creativecommons.org/publicdomain/zero/1.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-gruyter