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 inlammatory 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 inlammation and proin-lammatory signaling. We found increased activation of proinlam-matory 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-1ß cleavage and activation. The aggravated lung inflammatory signaling in Lyn-/- mice was associated with increased production of proinlammatory 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 inlammation.
|Journal||American Journal of Physiology - Lung Cellular and Molecular Physiology|
|State||Published - 2015|
Bibliographical notePublisher Copyright:
© 2015 the American Physiological Society.
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Physiology (medical)
- Cell Biology