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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.
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.
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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