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.
