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

A Hozumi1, Y Nishimura, T Nishiuma

  • 1First Department of Internal Medicine, Kobe University School of Medicine, Kobe 650-0017, Japan.

Insights

Tumor necrosis factor-alpha (TNF-alpha) induces matrix metalloproteinase-9 (MMP-9) in airway cells, mediated by nuclear factor-kappa B (NF-kappa B). Interleukin-1 beta did not induce MMP-9, but influenced its inhibitor.

Area of Science:

  • Cellular and Molecular Biology
  • Immunology
  • Respiratory Medicine

Background:

  • Proinflammatory cytokines play a role in airway inflammation.
  • Matrix metalloproteinase-9 (MMP-9) is implicated in airway remodeling and disease.
  • The role of specific cytokines in MMP-9 regulation in bronchial epithelial cells requires clarification.

Purpose of the Study:

  • To investigate the role of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) in regulating matrix metalloproteinase-9 (MMP-9) expression.
  • To determine if the transcription factor nuclear factor-kappa B (NF-kappa B) mediates TNF-alpha-induced MMP-9 expression in human bronchial epithelial cells.

Main Methods:

  • Human bronchial epithelial cells were treated with TNF-alpha and IL-1 beta.
  • MMP-9 protein and mRNA levels were assessed.
  • Activation of NF-kappa B was evaluated.
  • Inhibitory effects of pyrrolidine dithiocarbamate, N-acetyl-L-cysteine, and curcumin were tested.

Main Results:

  • TNF-alpha significantly induced MMP-9 expression at both protein and mRNA levels.
  • IL-1 beta did not induce MMP-9 but affected the induction of its inhibitor, tissue inhibitor of metalloproteinase-1.
  • TNF-alpha-induced MMP-9 expression and NF-kappa B activation were suppressed by pyrrolidine dithiocarbamate and N-acetyl-L-cysteine, but not by curcumin.

Conclusions:

  • TNF-alpha is a key inducer of MMP-9 in human bronchial epithelial cells.
  • The induction of MMP-9 by TNF-alpha is mediated through the NF-kappa B signaling pathway.
  • These findings contribute to understanding the molecular mechanisms underlying airway inflammation and remodeling.

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