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FEBS Lett. 2000 May 4;473(1):113-8.

Wortmannin inhibits activation of nuclear transcription factors NF-kappaB and activated protein-1 induced by lipopolysaccharide and phorbol ester.

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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.

Abstract

Whether all inflammatory agents activate nuclear transcription factors NF-kappaB 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-kappaB and AP-1 by different inflammatory agents. Wortmannin blocked NF-kappaB 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-kappaB correlated with abrogation of the degradation of IkappaBalpha and of NF-kappaB-dependent reporter gene transcription. Thus, the mechanism of NF-kappaB and AP-1 activation by lipopolysaccharide and phorbol ester involves PI-3K.

PMID:
10802070
DOI:
10.1016/s0014-5793(00)01501-5
[Indexed for MEDLINE]
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