Wortmannin inhibits activation of nuclear transcription factors NF‐κB and activated protein‐1 induced by lipopolysaccharide and phorbol ester

FEBS Letters

Manna, Sunil K¹  Aggarwal, Bharat B¹ 

[1] Cytokine Research Laboratory, Department of Bioimmunotherapy, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, P.O. Box 143, Houston, TX 77030, USA

关键词: Lipopolysaccharide;    Phorbol ester;    Nuclear transcription factor-κB;    Activated protein-1;    Wortmannin;    Phosphatidylinositol-3-kinase;    LPS;    lipopolysaccharide;    PMA;    phorbol ester;    OA;    okadaic acid;    TNF;    tumor necrosis factor;    AP-1;    activated protein-1;    IL-1;    interleukin-1;    SA-LPS;    serum-activated LPS;    NF-κB;    nuclear transcription factor-κB;    IκB;    inhibitory subunit of NF-κB;    EMSA;    electrophoretic mobility shift assay;    CAT;    chloramphenicol acetyltransferase;    PI-3K;    phosphatidylinositol-3-kinase;   

DOI  :  10.1016/S0014-5793(00)01501-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Whether all inflammatory agents activate nuclear transcription factors NF-κB and activated protein-1 (AP-1) through the same mechanism is not known. We examined the effect of the phosphatidylinositol-3-kinase (PI-3K) inhibitor wortmannin on the activation of NF-κB and AP-1 by different inflammatory agents. Wortmannin blocked NF-κB and AP-1 activation by lipopolysaccharide and phorbol ester but had minimal effect on activation by hydrogen peroxide, ceramide, okadaic acid and tumor necrosis factor. Inhibition of NF-κB correlated with abrogation of the degradation of IκBα and of NF-κB-dependent reporter gene transcription. Thus, the mechanism of NF-κB and AP-1 activation by lipopolysaccharide and phorbol ester involves PI-3K.

【 授权许可】

Unknown