• Rong Gao, Zhongsen Ma, Mengshi Ma, Jinyan Yu, Jiao Chen, Zhenyu Li, Sreerama Shetty, and Jian Fu.
• 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;
• Am. J. Physiol. Lung Cell Mol. Physiol. 2015 Dec 1; 309 (11): L1376-81.

AbstractOverwhelming 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. Copyright © 2015 the American Physiological Society.

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