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

• Published in: American journal of physiology. Lung cellular and molecular physiology Vol. 281; no. 6; pp. 1444 - L1452
• Main Authors: Hozumi, Atsuko, Nishimura, Yoshihiro, Nishiuma, Teruaki, Kotani, Yoshikazu, Yokoyama, Mitsuhiro
• Format: Journal Article
• Language: English
• Published: United States 01.12.2001
• Subjects: 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
• ISSN: 1040-0605; 1522-1504
• DOI: 10.1152/ajplung.2001.281.6.l1444

First Department of Internal Medicine, Kobe University School of Medicine, Kobe 650-0017, Japan In this study, we determined whether the proinflammatory cytokines tumor necrosis factor (TNF)- and interleukin-1 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)- B. We demonstrated that TNF- induced MMP-9 at both the protein and mRNA levels in human bronchial epithelial cells and that interleukin-1 did not. In contrast, induction of the tissue inhibitor of metalloproteinase-1 by TNF- was less than that of interleukin-1 . Increased expression of MMP-9 and NF- B activation induced by TNF- were inhibited by pyrrolidine dithiocarbamate and N -acetyl- L -cysteine but were not inhibited by curcumin. These results suggest that TNF- induces the expression of MMP-9 in human bronchial epithelial cells and that this induction is mediated via the NF- B-mediated pathway. matrix metalloproteinase-2; matrix metalloproteinase-9; tumor necrosis factor- ; nuclear factor- B; proinflammatory cytokine; airway inflammation