Genetic disruption of protein kinase Cδ reduces endotoxin-induced lung injury

Chichger, Havovi, Grinnell, Katie L., Casserly, Brian, Chung, Chun-Shiang, Braza, Julie, Lomas-Neira, Joanne, Ayala, Alfred, Rounds, Sharon, Klinger, James R. and Harrington, Elizabeth O. (2012) Genetic disruption of protein kinase Cδ reduces endotoxin-induced lung injury. American Journal of Physiology - Lung Cellular and Molecular Physiology, 303 (10). pp. 880-888. ISSN 1522-1504

Full text not available from this repository.

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 (kf) or wet-to-dry weight ratios between PKCδ+/+ and PKCδ−/− mice. However, at 24 h after exposure to LPS, the kf 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 kf 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.

Item Type:	Journal Article
Keywords:	endothelium, pulmonary edema, lipopolysaccharide, acute lung injury
Faculty:	ARCHIVED Faculty of Science & Technology (until September 2018)
Depositing User:	Repository Admin
Date Deposited:	01 Jun 2016 08:43
Last Modified:	09 Sep 2021 16:16
URI:	https://arro.anglia.ac.uk/id/eprint/611360

Actions (login required)

Edit Item