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ADAM17 mediates MMP9 expression in lung epithelial cells.


ABSTRACT: The purposes were to study the role of lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-?/nuclear factor-?B (NF-?B) signaling in matrix metalloproteinase 9 (MMP9) expression in A549 cells and to investigate the effects of lentivirus-mediated RNAi targeting of the disintegrin and metalloproteinase 17 (ADAM17) gene on LPS-induced MMP9 expression. MMP9 expression induced by LPS in A549 cells was significantly increased in a dose- and time-dependent manner (p<0.05). Pyrrolidine dithiocarbamate (PDTC) and a TNFR1 blocking peptide (TNFR1BP) significantly inhibited LPS-induced MMP9 expression in A549 cells (p<0.05). TNFR1BP significantly inhibited LPS-induced TNF-? production (p<0.05). Both PDTC and TNFR1BP significantly inhibited the phosphorylation of I?B? and expression of phosphorylation p65 protein in response to LPS (p<0.05), and the level of I?B? in the cytoplasm was significantly increased (p<0.05). Lentivirus mediated RNA interference (RNAi) significantly inhibited ADAM17 expression in A549 cells. Lentivirus-mediated RNAi targeting of ADAM17 significantly inhibited TNF-? production in the supernatants (p<0.05), whereas the level of TNF-? in the cells was increased (p<0.05). Lentiviral ADAM17 RNAi inhibited MMP9 expression, I?B? phosphorylation and the expression of phosphorylation p65 protein in response to LPS (p<0.05). PDTC significantly inhibited the expression of MMP9 and the phosphorylation of I?B?, as well as the expression of phosphorylation p65 protein in response to TNF-? (p<0.05). Lentiviral RNAi targeting of ADAM17 down-regulates LPS-induced MMP9 expression in lung epithelial cells via inhibition of TNF-?/NF-?B signaling.

SUBMITTER: Li YQ 

PROVIDER: S-EPMC3544892 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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ADAM17 mediates MMP9 expression in lung epithelial cells.

Li Ya-qing YQ   Yan Jian-ping JP   Xu Wu-lin WL   Wang Hong H   Xia Ying-jie YJ   Wang Hui-jun HJ   Zhu Yue-yan YY   Huang Xiao-jun XJ  

PloS one 20130114 1


The purposes were to study the role of lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α/nuclear factor-κB (NF-κB) signaling in matrix metalloproteinase 9 (MMP9) expression in A549 cells and to investigate the effects of lentivirus-mediated RNAi targeting of the disintegrin and metalloproteinase 17 (ADAM17) gene on LPS-induced MMP9 expression. MMP9 expression induced by LPS in A549 cells was significantly increased in a dose- and time-dependent manner (p<0.05). Pyrrolidine dithiocar  ...[more]

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