Inhibition of interleukin‐6 signaling by galiellalactone

FEBS Letters

Anke, Timm²  Weidler, Marcus¹  Erkel, Gerhard²  Rether, Jan² 

[1] Bayer AG, ZF-BTM, Geb. Q18, D-51368 Leverkusen, Germany;Institut für Biotechnologie und Wirkstoff-Forschung e.V. (IBWF), Erwin-Schrödinger-Str. 56, D-67663 Kaiserslautern, Germany

关键词: Galiellalactone;    Acute phase response;    IL-6 signaling;    Inhibitor;    APP;    acute phase protein;    AP-1;    activating protein-1;    IL-6;    interleukin-6;    IFN-γ;    interferon-γ;    NF-κB;    nuclear factor κB;    STAT;    signal transducer and activator of transcription;    TNF-α;    tumor necrosis factor-α;    TPA;    12-O-tetradecanoylphorbol-13-acetate;   

DOI  :  10.1016/S0014-5793(00)02115-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

A search for inhibitors of the IL-6-mediated signal transduction in HepG2 cells using secreted alkaline phosphatase (SEAP) as reporter gene resulted in the isolation of galiellalactone (1) from fermentations of the ascomycete strain A111-95. Galiellalactone inhibits the IL-6-induced SEAP expression with IC₅₀ values of 250–500 nM by blocking the binding of the activated Stat3 dimers to their DNA binding sites without inhibiting the tyrosine and serine phosphorylation of the Stat3 transcription factor. Due to its selective activity, galiellalactone may serve as a lead compound for the development of new therapeutic agents for diseases originating from the inappropriate expression of IL-6 and as molecular tool to dissect the JAK/STAT pathways.

【 授权许可】

Unknown