Induction of MMP-9 in normal human bronchial epithelial cells by TNF-alpha via NF-kappa B-mediated pathway

Am J Physiol Lung Cell Mol Physiol. 2001 Dec;281(6):L1444-52. doi: 10.1152/ajplung.2001.281.6.L1444.

Abstract

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)-kappa B. 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-1 beta. Increased expression of MMP-9 and NF-kappa B 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-kappa B-mediated pathway.

MeSH terms

  • Acetylcysteine / pharmacology
  • Antioxidants / pharmacology
  • Bronchi / cytology
  • Cells, Cultured
  • Free Radical Scavengers / pharmacology
  • Humans
  • Interleukin-1 / pharmacology
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism*
  • NF-kappa B / metabolism*
  • Pneumonia / immunology
  • Pneumonia / metabolism
  • Pyrrolidines / pharmacology
  • Respiratory Mucosa / cytology
  • Respiratory Mucosa / drug effects
  • Respiratory Mucosa / enzymology*
  • Thiocarbamates / pharmacology
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology*

Substances

  • Antioxidants
  • Free Radical Scavengers
  • Interleukin-1
  • NF-kappa B
  • Pyrrolidines
  • Thiocarbamates
  • Tissue Inhibitor of Metalloproteinase-1
  • Tumor Necrosis Factor-alpha
  • pyrrolidine dithiocarbamic acid
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • Acetylcysteine