Linked Life Data

20724665

Source:http://linkedlifedata.com/resource/pubmed/id/20724665

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2011-1-12
pubmed:abstractText
Inflammation and proinflammatory mediators are activators of ?-PKC. In vitro, ?-PKC regulates proinflammatory signaling in neutrophils and endothelial and epithelial cells, cells that can contribute to lung tissue damage associated with inflammation. In this study, a specific ?-PKC TAT peptide inhibitor was used to test the hypothesis that inhibition of ?-PKC would attenuate lung injury in an animal model of ARDS. Experimental ARDS was induced in rats via 2CLP, a model of polymicrobial sepsis. Following 2CLP surgery, the ?-PKC TAT inhibitory peptide (2CLP+?-PKC TAT in PBS) or PBS (2CLP+PBS) was administered intratracheally. Controls consisted of SO, where animals underwent a laparotomy without 2CLP. Twenty-four hours after SO or 2CLP, blood, BALF, and lung tissue were collected. 2CLP induced ?-PKC phosphorylation in the lung within 24 h. Treatment with the ?-PKC TAT inhibitory peptide significantly decreased pulmonary ?-PKC phosphorylation, indicating effective inhibition of ?-PKC activation. Plasma and BALF levels of the chemokines CINC-1 and MIP-2 were elevated in 2CLP + PBS rats as compared with SO rats. Treatment with ?-PKC TAT reduced 2CLP-induced elevations in chemokine levels in BALF and plasma, suggesting that ?-PKC modulated chemokine expression. Most importantly, intratracheal administration of ?-PKC TAT peptide significantly attenuated inflammatory cell infiltration, disruption of lung architecture, and pulmonary edema associated with 2CLP. Thus, ?-PKC is an important regulator of proinflammatory events in the lung. Targeted inhibition of ?-PKC exerted a lung-protective effect 24 h after 2CLP.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1938-3673
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
89
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3-10
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Protection against sepsis-induced lung injury by selective inhibition of protein kinase C-? (?-PKC).
pubmed:affiliation
Temple University School of Medicine, 3307 North Broad St., PAH-206, Philadelphia, PA 19140, USA. laurie.kilpatrick@temple.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural