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

Whether all inflammatory agents activate nuclear transcription factors NF-kappa B 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 NP-kappa B and AP-1 by different inflammatory agents. Wortmannin blocked NF-kappa B 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-kappa B correlated with abrogation of the degradation of I kappa B alpha and of NF-kappa B-dependent reporter gene transcription. Thus, the mechanism of NP-kappa B and AP-1 activation by lipopolysaccharide: and phorbol ester involves PI-3K. (C) 2000 Federation of European Biochemical Societies.