Epilysin (matrix metalloproteinase-28) contributes to airway epithelial cell survival

Respir Res. 2011 Oct 31;12(1):144. doi: 10.1186/1465-9921-12-144.

Abstract

MMP28 is constitutively expressed by epithelial cells in many tissues, including the respiratory epithelium in the lung and keratinocytes in the skin. This constitutive expression suggests that MMP28 may serve a role in epithelial cell homeostasis. In an effort to determine its function in epithelial cell biology, we generated cell lines expressing wild-type or catalytically-inactive mutant MMP28 in two pulmonary epithelial cell lines, A549 and BEAS-2B. We observed that over-expression of MMP28 provided protection against apoptosis induced by either serum-deprivation or treatment with a protein kinase inhibitor, staurosporine. Furthermore, we observed increased caspase-3/7 activity in influenza-infected lungs from Mmp28-/- mice compared to wild-type mice, and this activity localized to the airway epithelium but was not associated with a change in viral load. Thus, we have identified a novel role of MMP28 in promoting epithelial cell survival in the lung.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / physiology
  • Cell Line
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Cell Survival / physiology*
  • Chick Embryo
  • Humans
  • Matrix Metalloproteinases, Secreted / biosynthesis
  • Matrix Metalloproteinases, Secreted / deficiency
  • Matrix Metalloproteinases, Secreted / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Protein Kinase Inhibitors / therapeutic use
  • Respiratory Mucosa / drug effects
  • Respiratory Mucosa / enzymology*
  • Staurosporine / therapeutic use

Substances

  • Apoptosis Regulatory Proteins
  • Protein Kinase Inhibitors
  • MMP28 protein, human
  • Matrix Metalloproteinases, Secreted
  • Staurosporine