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 Go6976, 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 Go6976, 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.
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This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Shin, Y., Yoon, SH., Choe, EY. et al. PMA-induced up-regulation of MMP-9 is regulated by a PKCα-NF-κB cascade in human lung epithelial cells. Exp Mol Med 39, 97–105 (2007). https://doi.org/10.1038/emm.2007.11
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DOI: https://doi.org/10.1038/emm.2007.11