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

Abstract

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.