Journal
PLOS ONE
Volume 8, Issue 1, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0051701
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Funding
- National Natural Science Foundation of China [No_81000016]
- Medical Science Foundation of Zhejiang Province [No_2008B007]
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The purposes were to study the role of lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-alpha/nuclear factor-kappa B (NF-kappa 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-alpha production (p < 0.05). Both PDTC and TNFR1BP significantly inhibited the phosphorylation of I kappa B alpha and expression of phosphorylation p65 protein in response to LPS (p < 0.05), and the level of I kappa B alpha 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-alpha production in the supernatants (p < 0.05), whereas the level of TNF-alpha in the cells was increased (p < 0.05). Lentiviral ADAM17 RNAi inhibited MMP9 expression, I kappa B alpha 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 kappa B alpha, as well as the expression of phosphorylation p65 protein in response to TNF-alpha (p < 0.05). Lentiviral RNAi targeting of ADAM17 down-regulates LPS-induced MMP9 expression in lung epithelial cells via inhibition of TNF-alpha/NF-kappa B signaling.
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