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

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.