Vol 4: Interferon protects against lethal endotoxic and septic shock through SIRT1 upregulation.Report as inadecuate



 Vol 4: Interferon protects against lethal endotoxic and septic shock through SIRT1 upregulation.


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This article is from Scientific Reports, volume 4.AbstractLipopolysaccharide 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.



Author: Yoo, Chae-Hwa; Yeom, Ji-Hyun; Heo, Jin-Ju; Song, Eun-Kyung; Lee, Sang-Il; Han, Myung-Kwan

Source: https://archive.org/







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