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TNF‐α‐induced MMP‐9 expression via Src, EGFR, Akt, p300, NF‐κB, and histone acetylation in tracheal smooth muscle cells
Author(s) -
Lee ChiangWen,
Yang ChuenMao
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1443-d
Subject(s) - protein kinase b , phosphorylation , curcumin , chemistry , nf κb , pi3k/akt/mtor pathway , tumor necrosis factor alpha , cancer research , matrix metalloproteinase , ly294002 , proto oncogene tyrosine protein kinase src , microbiology and biotechnology , acetylation , signal transduction , biology , endocrinology , biochemistry , gene
TNF‐α has been shown to induce matrix metalloproteinase (MMP)‐9 production in various tissues. However, the mechanisms underlying TNF‐α‐induced MMP‐9 expression in human tracheal smooth muscle cells (HTSMCs) remain unclear. Here, the roles of growth factor receptors, NF‐κB, and p300 in TNF‐α‐induced MMP‐9 production were investigated in HTSMCs. TNF‐α‐induced expression of MMP‐9 and phosphorylation of Src, EGFR, and Akt were significantly attenuated by the inhibitors of Src (PP1), EGFR (AG1478), and PI3‐K (LY294002). TNF‐α‐induced MMP‐9 production and NF‐κB translocation into the nucleus were blocked by a NF‐κB inhibitor helenalin. TNF‐α‐induced MMP‐9 expression was blocked by a specific inhibitor of p300, curcumin, indicating that phosphorylation of Akt was translocated into the nucleus and interacted with p300, acetyl‐histone (H3) and NF‐κB p65 inhibited by the LY294002 and curcumin. Finally, ChIP assay revealed that TNF‐α induced association of NF‐κB p65, p300, and histone H3 with the mmp‐9 promoter mediated through a PI3K/Akt dependent pathway.