Exp Mol Med.  2007 Feb;39(1):97-105.

PMA-induced up-regulation of MMP-9 is regulated by a PKCalpha-NF-kappaB cascade in human lung epithelial cells

• Shin YH
• Yoon SH
• Choe EY
• Cho SH
• Woo CH
• Rho JY
• Kim JH

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.

Keyword

asthma; bronchial hyperreactivity; epithelial cells; matrix metalloproteinase 9; NF-kappaB; protein kinase C-alpha

MeSH Terms

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