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Sci Rep. 2014 Feb 27;4:4220. doi: 10.1038/srep04220.

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

Author information

1
1] Department of Microbiology, Chonbuk National University Medical School, Jeonju 561-182, Republic of Korea [2].
2
Department of Microbiology, Chonbuk National University Medical School, Jeonju 561-182, Republic of Korea.
3
Department of Internal Medicine, Institute of Health Science, Gyeongsang National University College of Medicine, Jinju 660-702, Republic of Korea.
4
1] Department of Microbiology, Chonbuk National University Medical School, Jeonju 561-182, Republic of Korea [2] Institute for Medical Science, Chonbuk National University Medical School, Jeonju 561-182, Republic of Korea.

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-STAT) pathway in mouse bone marrow derived macrophages. In vivo treatment of interferon β protects against lethal endotoxic and septic shock, which is abrogated by infection with dominant negative SIRT1-expressing adenovirus. Our work suggests that both SIRT1 and SIRT1-inducing cytokines are useful targets for treating patients with sepsis.

PMID:
24573134
PMCID:
PMC3936230
DOI:
10.1038/srep04220
[Indexed for MEDLINE]
Free PMC Article
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