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KMID : 0620920070390010097
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Experimental & Molecular Medicine
2007 Volume.39 No. 1 p.97 ~ p.105
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PMA-induced up-regulation of MMP-9 is regulated by a PKCa-NF-kB cascade in human lung epithelial cells
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Shin Young-Hyun
Kim Jae-Hong
Yoon Sun-Hee
Choi Eun-Young
Choi Sung-Hoon
Woo Chang-Hoon
Rho Jee-Yeon
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Abstract
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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 Ca (PKCa)-dependent signaling cascade in BEAS-2B human lung epithelial cells. Pretreatment with either GF109203X, a general PKC inhibitor, or Go6976, a PKCa/b isozyme inhibitor, inhibited PMA-induced activation of the MMP-9 promoter, as did transient transfection with PKCa antisense oligonuclotides. PMA activated NF-kB by phosphorylating IkB in these cells and this was also inhibited by GF109203X and Go6976, suggesting that PKCa acts as an upstream regulator of NF-kB in PMA-induced MMP-9 induction. Our results indicate that a “PKCa-NF- kB”-dependent cascade is involved in the signaling leading to PMA-induced MMP-9 expression in the lung epithelium.
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KEYWORD
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asthma, bronchial hyperreactivity, epithelial cells, matrix metalloproteinase 9, NF-κB, protein kinase C-α
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