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

• Published in: Experimental & molecular medicine 2007-02, Vol.39 (1), p.97-105
• Main Authors: Shin, Young Hyun, Yoon, Sun-Hee, Choe, Eun-Young, Cho, Sung-Hoon, Woo, Chang-Hoon, Rho, Jee-Yeon, Kim, Jae-Hong
• Format: Article
• Language: English
• ISSN: 2092-6413; 1226-3613; 2092-6413
• DOI: 10.1038/emm.2007.11

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 C alpha (PKC alpha )-dependent signaling cascade in BEAS-2B human lung epithelial cells. Pretreatment with either GF109203X, a general PKC inhibitor, or Go6976, a PKC alpha / beta isozyme inhibitor, inhibited PMA-induced activation of the MMP-9 promoter, as did transient transfection with PKC alpha antisense oligonuclotides. PMA activated NF- Kappa B by phosphorylating I Kappa B in these cells and this was also inhibited by GF109203X and Go6976, suggesting that PKC alpha acts as an upstream regulator of NF- Kappa B in PMA-induced MMP-9 induction. Our results indicate that a "PKC alpha -NF- Kappa B"-dependent cascade is involved in the signaling leading to PMA-induced MMP-9 expression in the lung epithelium.