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

Whether all inflammatory agents activate nuclear transcription factors NF-k appa B and activated protein-1 (AP-1) through the same mechanism is not kno wn. We examined the effect of the phosphatidylinositol-3-kinase (PI-3K) inh ibitor wortmannin on the activation of NP-kappa B and AP-1 by different inf lammatory agents. Wortmannin blocked NF-kappa B and AP-1 activation by lipo polysaccharide and phorbol ester but had minimal effect on activation by hy drogen peroxide, ceramide, okadaic acid and tumor necrosis factor, Inhibiti on 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 m echanism of NP-kappa B and AP-1 activation by lipopolysaccharide: and phorb ol ester involves PI-3K. (C) 2000 Federation of European Biochemical Societ ies.