Sirt1 restrains lung inflammasome activation in a murine model of sepsis

摘要: Excessive inflammation is a major cause of organ damage during sepsis. The elderly are highly susceptible to sepsis-induced injury. Sirt1 expression reduced aging. In the present study, we investigated role Sirt1, histone deacetylase, in controlling inflammatory responses murine sepsis model induced by cecal ligation and puncture (CLP). We examined lung signaling inducible knockout (Sirt1(-/-)) mice wild-type littermates (Sirt1(+/+)) after CLP. Our results demonstrated that deficiency led severe To further investigate molecular mechanisms regulation sepsis, conducted series experiments assess inflammasome activation detected increased including NF-κB, signal transducer activator transcription 3, ERK1/2 Sirt1(-/-) Furthermore, activity was CLP, as IL-1β caspase-7 cleavage activation. Aggravated associated with production proinflammatory mediators, ICAM-1 high-mobility group box 1, disruption tight junctions adherens junctions, dramatic reduction claudin-1 vascular endothelial-cadherin expression, which upregulation matrix metallopeptidase 9 expression. summary, our suggest suppresses acute pathway.