Interferon β protects against lethal endotoxic and septic shock through SIRT1 upregulation.

ABSTRACT: Lipopolysaccharide (LPS), an endotoxin derived from gram-negative bacteria, promotes the secretion of proinflammatory cytokines and mediates endotoxemia through activation of mitogen activated protein kinases, NF-κB, and interferon regulatory factor-3. Silent information regulator transcript-1 (SIRT1), an NAD-dependent deacetylase, mediates NF-κB deacetylation, and inhibits its function. SIRT1 may affect LPS-mediated signaling pathways and endotoxemia. Here we demonstrate that SIRT1 blocks LPS-induced secretion of interleukin 6 and tumor necrosis factor α in murine macrophages, and protects against lethal endotoxic and septic shock in mice. We also demonstrate that interferon β increases SIRT1 expression by activating the Janus kinase--signal transducer and activator of transcription (JAK-

SUBMITTER: Yoo CH 

PROVIDER: S-EPMC3936230 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature