Induction of MMP-9 in normal human bronchial epithelial cells by TNF-alpha via NF-kappa B-mediated pathway.
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.
Hozumi
A
A
First Department of Internal Medicine, Kobe University School of Medicine, Kobe 650-0017, Japan.
Nishimura
Y
Y
Nishiuma
T
T
Kotani
Y
Y
Yokoyama
M
M
D000111:Acetylcysteine / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D001980:Bronchi / Q000166:cytology; D002478:Cells, Cultured; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D011014:Pneumonia / Q000276:immunology / Q000378:metabolism; D011759:Pyrrolidines / Q000494:pharmacology; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D013859:Thiocarbamates / Q000494:pharmacology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000975:Antioxidants; D016166:Free Radical Scavengers; D007375:Interleukin-1; D016328:NF-kappa B; D011759:Pyrrolidines; D013859:Thiocarbamates; D019715:Tissue Inhibitor of Metalloproteinase-1; D014409:Tumor Necrosis Factor-alpha; C020972:pyrrolidine dithiocarbamic acid; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D000111:Acetylcysteine