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

• Published in: Experimental & molecular medicine pp. 97 - 105
• Main Authors: 신영현, 조성훈, 윤선희, 김재홍, 오지연, 우창훈, 조은영
• Format: Journal Article
• Language: English
• Published: 생화학분자생물학회 01.02.2007
• Subjects: 생화학
• ISSN: 1226-3613; 2092-6413

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 Cα (PKCα)-dependent signaling cascade in BEAS-2B human lung epithelial cells. Pretreatment with either GF109203X, a general PKC inhibitor, or Gö6976, a PKCα/β isozyme inhibitor, inhibited PMA-induced activation of the MMP-9 promoter, as did transient transfection with PKCα antisense oligonuclotides. PMA activated NF-κB by phosphorylating IκB in these cells and this was also inhibited by GF109203X and Gö6976, suggesting that PKCα acts as an upstream regulator of NF-κB in PMA-induced MMP-9 induction. Our results indicate that a “PKCα-NF- κB”-dependent cascade is involved in the signaling leading to PMA-induced MMP-9 expression in the lung epithelium. KCI Citation Count: 71