| RRC ID |
19140
|
| 著者 |
Chichger H, Grinnell KL, Casserly B, Chung CS, Braza J, Lomas-Neira J, Ayala A, Rounds S, Klinger JR, Harrington EO.
|
| タイトル |
Genetic disruption of protein kinase Cδ reduces endotoxin-induced lung injury.
|
| ジャーナル |
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.
|
| 巻・号 |
303(10)
|
| ページ |
L880-8
|
| 公開日 |
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
|
| 引用数 |
22
|
|
WOS 分野
|
RESPIRATORY SYSTEM
PHYSIOLOGY
|
| リソース情報 |
| 実験動物マウス |
RBRC00457 |
