PMA-induced up-regulation of MMP-9 is regulated by a PKCalpha-NF-kappaB cascade in human lung epithelial cells
Experimental & Molecular Medicine
;
: 97-105, 2007.
Article
in English
| WPRIM
| ID: wpr-37551
ABSTRACT
Expression of matrix metalloproteinase-9 (MMP-9) is associated with airway remodeling and tissue injury in asthma. However, little is known about how MMP-9 is up-regulated in airway epithelial cells. In this study, we show that phorbol myristate acetate (PMA) induces MMP-9 expression via a protein kinase Calpha(PKCalpha)-dependent signaling cascade in BEAS-2B human lung epithelial cells. Pretreatment with either GF109203X, a general PKC inhibitor, or Go6976, a PKCalpha/beta isozyme inhibitor, inhibited PMA-induced activation of the MMP-9 promoter, as did transient transfection with PKCalpha antisense oligonuclotides. PMA activated NF-kappaB by phosphorylating IkappaB in these cells and this was also inhibited by GF109203X and Go6976, suggesting that PKCalpha acts as an upstream regulator of NF-kappaB in PMA-induced MMP-9 induction. Our results indicate that a "PKCalpha-NF-kappaB"-dependent cascade is involved in the signaling leading to PMA-induced MMP-9 expression in the lung epithelium.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Tetradecanoylphorbol Acetate
/
Up-Regulation
/
Cell Line
/
NF-kappa B
/
Matrix Metalloproteinase 9
/
Epithelial Cells
/
Protein Kinase C-alpha
/
Lung
Limits:
Humans
Language:
English
Journal:
Experimental & Molecular Medicine
Year:
2007
Type:
Article
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