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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred

12 Issues per year


IMPACT FACTOR 2016: 3.273

CiteScore 2016: 3.01

SCImago Journal Rank (SJR) 2016: 1.679
Source Normalized Impact per Paper (SNIP) 2016: 0.800

Online
ISSN
1437-4315
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Volume 388, Issue 6 (Jun 2007)

Issues

Inhibition of inducible tumor necrosis factor-α expression by the fungal epipolythiodiketopiperazine gliovirin

Jan Rether
  • 1Institut für Biotechnologie und Wirkstoff-Forschung e.V., Erwin-Schrödinger-Str. 56, D-67663 Kaiserslautern, Germany
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/ Annegret Serwe
  • 2Department of Biotechnology, University of Kaiserslautern, Paul-Ehrlich-Str. 23, D-67663 Kaiserslautern, Germany
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/ Timm Anke
  • 3Department of Biotechnology, University of Kaiserslautern, Paul-Ehrlich-Str. 23, D-67663 Kaiserslautern, Germany
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/ Gerhard Erkel
  • 4Department of Biotechnology, University of Kaiserslautern, Paul-Ehrlich-Str. 23, D-67663 Kaiserslautern, Germany
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Published Online: 2007-06-01 | DOI: https://doi.org/10.1515/BC.2007.066

Abstract

TNF-α is a major pro-inflammatory cytokine that regulates further cytokine induction, especially of IL-1 and IL-6, in many human diseases including cancer, inflammation and immune disorders. In a search for new inhibitors of inducible TNF-α promoter activity and expression, cultures of the imperfect fungus Trichoderma harzianum were found to produce gliovirin, a previously isolated epipolythiodiketopiperazine. Gliovirin inhibited inducible TNF-α promoter activity and synthesis in LPS/IFN-γ-stimulated macrophages/monocytes and Jurkat T-cells, co-stimulated with 12-O-tetradecanoylphorbol-13-acetate (TPA)/ionomycin, in a dose-dependent manner, with IC50 values ranging from 0.21 to 2.1 μM (0.1–1 μg/ml). Studies on the mode of action revealed that gliovirin suppresses TNF-α synthesis by inhibiting the activation of extracellular signal-regulated kinase (ERK), thereby blocking the pathway leading to activation of the transcription factors AP-1 and NF-κB, the latter of which is involved in the inducible expression of many pro-inflammatory genes. Gliovirin also significantly reduced TPA/ionomycin-induced IL-2 mRNA levels and synthesis in Jurkat cells at low micromolar concentrations.

Keywords: ERK; gliovirin; IL-2 synthesis; inhibitor; NF-κB; TNF-α synthesis

About the article

Corresponding author


Received: 2006-11-24

Accepted: 2007-03-04

Published Online: 2007-06-01


Citation Information: Biological Chemistry, ISSN (Online) 14316730, ISSN (Print) 14374315, DOI: https://doi.org/10.1515/BC.2007.066.

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