4.5 Article

Induction of MMP-9 in normal human bronchial epithelial cells by TNF-α via NF-κB-mediated pathway

Publisher

AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajplung.2001.281.6.L1444

Keywords

matrix metalloproteinase-2; matrix metalloproteinase-9; tumor necrosis factor-alpha; nuclear factor-kappa B; proinflammatory cytokine; airway inflammation

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In this study, we determined whether the proinflammatory cytokines tumor necrosis factor (TNF)-alpha and interleukin-1 beta contribute to the regulation of matrix metalloproteinase (MMP)-9 in human bronchial epithelial cells and whether the induction of MMP-9 is regulated by the transcription factor nuclear factor (NF)-kappaB. We demonstrated that TNF-alpha induced MMP-9 at both the protein and mRNA levels in human bronchial epithelial cells and that interleukin-1 beta did not. In contrast, induction of the tissue inhibitor of metalloproteinase-1 by TNF-alpha was less than that of interleukin-1b. Increased expression of MMP-9 and NF-kappaB activation induced by TNF-alpha were inhibited by pyrrolidine dithiocarbamate and N-acetyl-L-cysteine but were not inhibited by curcumin. These results suggest that TNF-alpha induces the expression of MMP-9 in human bronchial epithelial cells and that this induction is mediated via the NF-kappaB-mediated pathway.

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