title: Deletion of Src family kinase Lyn aggravates endotoxin-induced lung inflammation.
abstract: Overwhelming acute inflammation often leads to tissue damage during endotoxemia. In the present study, we investigated the role of Lyn, a member of the Src family tyrosine kinases, in modulating inflammatory responses in a murine model of endotoxemia. We examined lung inflammatory signaling in Lyn knockout (Lyn(-/-)) mice and wild-type littermates (Lyn(+/+)) during endotoxemia. Our data indicate that Lyn deletion aggravates endotoxin-induced pulmonary inflammation and proinflammatory signaling. We found increased activation of proinflammatory transcription factor NF-κB in the lung tissues of Lyn(-/-) mice after endotoxin challenge. Furthermore, during endotoxemia, the lung tissues of Lyn(-/-) mice showed increased inflammasome activation indicated by augmented caspase-1 and IL-1β cleavage and activation. The aggravated lung inflammatory signaling in Lyn(-/-) mice was associated with increased production of proinflammatory mediators and elevated matrix metallopeptidase 9 and reduced VE-cadherin levels. Our results suggest that Lyn kinase modulates inhibitory signaling to suppress endotoxin-induced lung inflammation.
authors.affiliation: The Second Hospital of Jilin University, Changchun, China; Center for Research on Environmental Disease, University of Kentucky, Lexington, Kentucky; Graduate Center for Toxicology, University of Kentucky, Lexington, Kentucky;
authors.forename: Rong
authors.initials: R
authors.lastname: Gao
authors.affiliation: The Second Hospital of Jilin University, Changchun, China;
authors.forename: Zhongsen
authors.initials: Z
authors.lastname: Ma
authors.affiliation: The Second Hospital of Jilin University, Changchun, China; Center for Research on Environmental Disease, University of Kentucky, Lexington, Kentucky;
authors.forename: Mengshi
authors.initials: M
authors.lastname: Ma
authors.affiliation: The Second Hospital of Jilin University, Changchun, China; Center for Research on Environmental Disease, University of Kentucky, Lexington, Kentucky;
authors.forename: Jinyan
authors.initials: J
authors.lastname: Yu
authors.affiliation: Center for Research on Environmental Disease, University of Kentucky, Lexington, Kentucky;
authors.forename: Jiao
authors.initials: J
authors.lastname: Chen
authors.affiliation: Division of Cardiovascular Medicine, College of Medicine, University of Kentucky, Lexington, Kentucky; and.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Li
authors.affiliation: Center for Biomedical Research, University of Texas Health Science Center at Tyler, Tyler, Texas.
authors.forename: Sreerama
authors.initials: S
authors.lastname: Shetty
authors.affiliation: Center for Research on Environmental Disease, University of Kentucky, Lexington, Kentucky; Graduate Center for Toxicology, University of Kentucky, Lexington, Kentucky; jian.fu@uky.edu.
authors.forename: Jian
authors.initials: J
authors.lastname: Fu
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D020170:Caspase 1 / Q000378:metabolism; D017353:Gene Deletion; D058847:Inflammasomes / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides; D008168:Lung / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D011014:Pneumonia / Q000201:enzymology* / Q000473:pathology*; D019061:src-Family Kinases / Q000172:deficiency / Q000378:metabolism*; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D020170:Caspase 1; D058847:Inflammasomes; D018836:Inflammation Mediators; D018799:Intercellular Adhesion Molecule-1; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D020780:Matrix Metalloproteinase 9; D016328:NF-kappa B; D019061:src-Family Kinases; D000099152:Cadherin 5; C060902:lyn protein-tyrosine kinase
keywords: inflammasome; inflammation; kinase; lung; lyn