PMA-induced up-regulation of MMP-9 is regulated by a PKCalpha-NF-kappaB cascade in human lung epithelial cells.
- Author:
Young Hyun SHIN
1
;
Sun Hee YOON
;
Eun Young CHOE
;
Sung Hoon CHO
;
Chang Hoon WOO
;
Jee Yeon RHO
;
Jae Hong KIM
Author Information
1. School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Korea. jhongkim@korea.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
asthma;
bronchial hyperreactivity;
epithelial cells;
matrix metalloproteinase 9;
NF-kappaB;
protein kinase C-alpha
- MeSH:
Up-Regulation/*drug effects;
Tetradecanoylphorbol Acetate/*pharmacology;
Protein Kinase C-alpha/*metabolism;
NF-kappa B/*metabolism;
Matrix Metalloproteinase 9/*metabolism;
Lung/drug effects/*metabolism;
Humans;
Epithelial Cells/drug effects/metabolism;
Cell Line
- From:Experimental & Molecular Medicine
2007;39(1):97-105
- CountryRepublic of Korea
- Language:English
-
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.
