Reference - Detail
| RRC ID | 19140 |
|---|---|
| Author | Chichger H, Grinnell KL, Casserly B, Chung CS, Braza J, Lomas-Neira J, Ayala A, Rounds S, Klinger JR, Harrington EO. |
| Title | Genetic disruption of protein kinase Cδ reduces endotoxin-induced lung injury. |
| Journal | Am J Physiol Lung Cell Mol Physiol |
| Abstract |
The pathogenesis of acute lung injury and acute respiratory distress syndrome is characterized by sequestration of leukocytes in lung tissue, disruption of capillary integrity, and pulmonary edema. PKCδ plays a critical role in RhoA-mediated endothelial barrier function and inflammatory responses. We used mice with genetic deletion of PKCδ (PKCδ(-/-)) to assess the role of PKCδ in susceptibility to LPS-induced lung injury and pulmonary edema. Under baseline conditions or in settings of increased capillary hydrostatic pressures, no differences were noted in the filtration coefficients (k(f)) or wet-to-dry weight ratios between PKCδ(+/+) and PKCδ(-/-) mice. However, at 24 h after exposure to LPS, the k(f) values were significantly higher in lungs isolated from PKCδ(+/+) than PKCδ(-/-) mice. In addition, bronchoalveolar lavage fluid obtained from LPS-exposed PKCδ(+/+) mice displayed increased protein and cell content compared with LPS-exposed PKCδ(-/-) mice, but similar changes in inflammatory cytokines were measured. Histology indicated elevated LPS-induced cellularity and inflammation within PKCδ(+/+) mouse lung parenchyma relative to PKCδ(-/-) mouse lungs. Transient overexpression of catalytically inactive PKCδ cDNA in the endothelium significantly attenuated LPS-induced endothelial barrier dysfunction in vitro and increased k(f) lung values in PKCδ(+/+) mice. However, transient overexpression of wild-type PKCδ cDNA in PKCδ(-/-) mouse lung vasculature did not alter the protective effects of PKCδ deficiency against LPS-induced acute lung injury. We conclude that PKCδ plays a role in the pathological progression of endotoxin-induced lung injury, likely mediated through modulation of inflammatory signaling and pulmonary vascular barrier function. |
| Volume | 303(10) |
| Pages | L880-8 |
| Published | 2012-11-15 |
| DOI | 10.1152/ajplung.00169.2012 |
| PII | ajplung.00169.2012 |
| PMID | 22983354 |
| PMC | PMC3517673 |
| MeSH | Acute Lung Injury / chemically induced Acute Lung Injury / enzymology* Acute Lung Injury / genetics Acute Lung Injury / pathology Animals Blood-Air Barrier / enzymology* Blood-Air Barrier / pathology Cytokines / genetics Cytokines / metabolism Gene Expression Regulation, Enzymologic / drug effects* Inflammation Mediators / metabolism Lipopolysaccharides / toxicity* Mice Mice, Knockout Protein Kinase C-delta / biosynthesis* Protein Kinase C-delta / genetics Pulmonary Edema / chemically induced Pulmonary Edema / enzymology Pulmonary Edema / genetics Pulmonary Edema / pathology Respiratory Distress Syndrome |
| IF | 4.418 |
| Times Cited | 22 |
| WOS Category | RESPIRATORY SYSTEM PHYSIOLOGY |
| Altmetric score |
オルトメトリクス指標項目
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| Total number of mentions | 0 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Mice | RBRC00457 |