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IL‐1β induces MMP‐9 expression associated with cell migration via a c‐Src‐dependent PDGFR/EGFR transactivation in A549 cells
Author(s) -
Yang Caleb M.,
Yang ChuenMao
Publication year - 2011
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.25.1_supplement.121.7
Subject(s) - transactivation , proto oncogene tyrosine protein kinase src , cancer research , protein kinase b , chemistry , a549 cell , pi3k/akt/mtor pathway , phosphorylation , ly294002 , tyrosine kinase , epidermal growth factor receptor , microbiology and biotechnology , tyrosine phosphorylation , signal transduction , receptor , biology , cell , gene expression , biochemistry , gene
IL‐1β has been shown to induce MMP‐9 expression which is regulated by MAPKs and NF‐κB in various cell types. IL‐1β also stimulates transactivation of growth factor receptors and PI3K/Akt, leading to the expression of inflammatory proteins. Here, we investigated whether these transactivation mechanisms participated in IL‐1β‐induced MMP‐9 expression in A549 cells. Inhibition of MMP‐9 expression by the inhibitors of Src (PP1), PDGFR (AG1296), and EGFR (AG1478) or transfection with siRNA of Src and Akt prevented IL‐1β‐induced cell migration in A549 cells. The involvement of these tyrosine kinases in these responses was mediated through phosphorylation of Src, PDGFR, or EGFR via the formation of Src/PDGFR or Src/EGFR complex which was attenuated by PP1. Moreover, IL‐1β‐induced MMP‐9 expression through EGFR transactivation was diminished by the inhibitors of MMPs and heparin‐binding EGF‐like factor (HB‐EGF), or neutralizing HB‐EGF antibody. Moreover, IL‐1β‐stimulated activation and translocation of Akt and NF‐κB (p65), and then the activated NF‐κB (p65) recruited to MMP‐9 promoter region, which was attenuated by pretreatment with LY294002. These results suggested that IL‐1β‐induced MMP‐9 expression and cell migration was mediated via transactivation of Src/EGFR/PDGFR/Akt/NF‐κB in A549.