STAT1-deficient mice are resistant to cecal ligation and puncture-induced septic shock.
STAT1-deficient mice are resistant to cecal ligation and puncture-induced septic shock.
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DOI：
10.1097/shk.0b013e318265a2ab
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发表时间：
2012-10
期刊：
影响因子：
--
通讯作者：
Sherwood ER
中科院分区：
文献类型：
--
作者：
Herzig D;Fang G;Toliver-Kinsky TE;Guo Y;Bohannon J;Sherwood ER
STAT1 is a member of the JAK-STAT signaling family and plays a key role in facilitating gene transcription in response to activation of the Type I and Type II interferon (IFN) receptors. TYK2 is essential for type I, but not type II, IFN-induced STAT1 activation. Previous studies show that STAT1-deficient mice are resistant to endotoxin-induced shock. The goal of the present study was to assess the response of STAT1-and TYK2-deficient mice to septic shock caused by cecal ligation and puncture (CLP). Endpoints included survival, core temperature, organ injury, systemic cytokine production and bacterial clearance. Results showed that survival rates were significantly higher in STAT1KO mice compared to wild type controls (80% vs 10%). The improved survival of STAT1KO mice was associated with less hypothermia, metabolic acidosis, hypoglycemia and hepatocellular injury. Plasma IL-6, MIP-2, CXCL10 and IFNα concentrations were significantly lower in STAT1KO mice than in wild type mice. In the absence of antibiotic treatment, blood and lung bacterial counts were significantly lower in STAT1KO mice than in controls. However, treatment with antibiotics ablated that difference. A survival advantage was not observed in TYK2-deficient mice compared to control. However, CLP-induced hypothermia and systemic IL-6 and CXCL10 production were significantly attenuated in TYK2-deficient mice. These results indicate that STAT1 activation is an important factor in the pathogenesis of CLP-induced septic shock and is associated with the development of systemic inflammation and organ injury. TYK2 activation also appears to contribute to CLP-induced inflammation, but to a lesser extent than STAT1.
