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Involvement of Protein Kinase C-δ in Vascular Permeability in Acute Lung Injury

  • Ahn, Jong J. (Department of Internal Medicine, Ulsan University Hospital, School of Medicine, University of Ulsan) ;
  • Jung, Jong P. (Department of Thoracic Surgery, Ulsan University Hospital, University of Ulsan College of Medicine) ;
  • Park, Soon E. (Department of Anesthesiology and Pain Medicine, Ulsan University Hospital, University of Ulsan College of Medicine) ;
  • Lee, Minhyun (Department of Anesthesiology and Pain Medicine, Ulsan University Hospital, University of Ulsan College of Medicine) ;
  • Kwon, Byungsuk (School of Biological Sciences, University of Ulsan) ;
  • Cho, Hong R. (Biomedical Research Center)
  • Received : 2015.06.23
  • Accepted : 2015.07.30
  • Published : 2015.08.31

Abstract

Pulmonary edema is a major cause of mortality due to acute lung injury (ALI). The involvement of protein kinase C-${\delta}$ (PKC-${\delta}$) in ALI has been a controversial topic. Here we investigated PKC-${\delta}$ function in ALI using PKC-${\delta}$ knockout (KO) mice and PKC inhibitors. Our results indicated that although the ability to produce proinflammatory mediators in response to LPS injury in PKC-${\delta}$ KO mice was similar to that of control mice, they showed enhanced recruitment of neutrophils to the lung and more severe pulmonary edema. PKC-${\delta}$ inhibition promoted barrier dysfunction in an endothelial cell layer in vitro, and administration of a PKC-${\delta}$-specific inhibitor significantly increased steady state vascular permeability. A neutrophil transmigration assay indicated that the PKC-${\delta}$ inhibition increased neutrophil transmigration through an endothelial monolayer. This suggests that PKC-${\delta}$ inhibition induces structural changes in endothelial cells, allowing extravasation of proteins and neutrophils.

Keywords

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