title: Epilysin (matrix metalloproteinase-28) contributes to airway epithelial cell survival.
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.
authors: Center for Lung Biology, Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of Washington, Seattle, WA, USA. manicone@u.washington.edu
authors: Anne M
authors: AM
authors: Manicone
authors: Susanna
authors: S
authors: Harju-Baker
authors: Laura K
authors: LK
authors: Johnston
authors: Ann J
authors: AJ
authors: Chen
authors: William C
authors: WC
authors: Parks
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D002642:Chick Embryo; D006801:Humans; D053505:Matrix Metalloproteinases, Secreted / Q000096:biosynthesis / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D020545:Respiratory Mucosa / Q000187:drug effects / Q000201:enzymology*; D019311:Staurosporine / Q000627:therapeutic use
chemical_list: D051017:Apoptosis Regulatory Proteins; D047428:Protein Kinase Inhibitors; C424663:MMP28 protein, human; D053505:Matrix Metalloproteinases, Secreted; D019311:Staurosporine