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Wortmannin inhibits activation of nuclear transcription factors NF‐κB and activated protein‐1 induced by lipopolysaccharide and phorbol ester
Author(s) -
Manna Sunil K,
Aggarwal Bharat B
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)01501-5
Subject(s) - wortmannin , lipopolysaccharide , phosphatidylinositol , phorbol , chemistry , transcription factor , nf κb , microbiology and biotechnology , protein kinase c , nfkb1 , phorbol ester , tumor necrosis factor alpha , signal transduction , biochemistry , biology , endocrinology , gene
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.