| First Author | Chichger H | Year | 2012 |
| Journal | Am J Physiol Lung Cell Mol Physiol | Volume | 303 |
| Issue | 10 | Pages | L880-8 |
| PubMed ID | 22983354 | Mgi Jnum | J:193660 |
| Mgi Id | MGI:5468909 | Doi | 10.1152/ajplung.00169.2012 |
| Citation | Chichger H, et al. (2012) Genetic disruption of protein kinase Cdelta reduces endotoxin-induced lung injury. Am J Physiol Lung Cell Mol Physiol 303(10):L880-8 |
| abstractText | 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. PKCdelta plays a critical role in RhoA-mediated endothelial barrier function and inflammatory responses. We used mice with genetic deletion of PKCdelta (PKCdelta(-/-)) to assess the role of PKCdelta 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 PKCdelta(+/+) and PKCdelta(-/-) mice. However, at 24 h after exposure to LPS, the k(f) values were significantly higher in lungs isolated from PKCdelta(+/+) than PKCdelta(-/-) mice. In addition, bronchoalveolar lavage fluid obtained from LPS-exposed PKCdelta(+/+) mice displayed increased protein and cell content compared with LPS-exposed PKCdelta(-/-) mice, but similar changes in inflammatory cytokines were measured. Histology indicated elevated LPS-induced cellularity and inflammation within PKCdelta(+/+) mouse lung parenchyma relative to PKCdelta(-/-) mouse lungs. Transient overexpression of catalytically inactive PKCdelta cDNA in the endothelium significantly attenuated LPS-induced endothelial barrier dysfunction in vitro and increased k(f) lung values in PKCdelta(+/+) mice. However, transient overexpression of wild-type PKCdelta cDNA in PKCdelta(-/-) mouse lung vasculature did not alter the protective effects of PKCdelta deficiency against LPS-induced acute lung injury. We conclude that PKCdelta plays a role in the pathological progression of endotoxin-induced lung injury, likely mediated through modulation of inflammatory signaling and pulmonary vascular barrier function. |
