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

YoungHyun Shin, Sun Hee Yoon, Eun Young Choe, Sung Hoon Cho, Chang Hoon Woo, Jee Yeon Rho, Jae-Hong Kim

Research output: Contribution to journalArticle

75 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)97-105
Number of pages9
JournalExperimental and Molecular Medicine
Volume39
Issue number1
Publication statusPublished - 2007 Feb 28

Keywords

  • Asthma
  • Bronchial hyperreactivity
  • Epithelial cells
  • Matrix metalloproteinase 9
  • NF-κB
  • Protein kinase C-α

ASJC Scopus subject areas

  • Biochemistry
  • Genetics

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