Disruption of the transient receptor potential vanilloid 1 can affect survival, bacterial clearance, and cytokine gene expression during murine sepsis.
Disruption of the transient receptor potential vanilloid 1 can affect survival, bacterial clearance, and cytokine gene expression during murine sepsis.
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瞬态受体电位香草素1的破坏会影响鼠败血症期间的生存，细菌清除率和细胞因子基因表达。
DOI：
10.1097/aln.0b013e318212515b
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发表时间：
2011-05
期刊：
影响因子：
8.8
通讯作者：
Quezado ZM
中科院分区：
文献类型：
--
作者：
Guptill V;Cui X;Khaibullina A;Keller JM;Spornick N;Mannes A;Iadarola M;Quezado ZM
Previous studies suggest that the transient receptor potential vanilloid-1 (TRPV1) has a role in sepsis but it is unclear whether its effect on survival and immune response is beneficial or harmful. We studied the effects of genetic (Trpv1-knock out vs. wild-type mice) and pharmacologic disruption of TRPV1 with resiniferatoxin (an agonist) or capsazepine (an antagonist) on mortality, bacterial clearance, and cytokine expression during lipopolysaccharide or cecal ligation and puncture (CLP)-induced sepsis. After CLP, genetic disruption of TRPV1 in Trpv1-knock out mice was associated with increased mortality risk [2.17 (1.23 to 3.81) hazard ratio (95% confidence interval), p=0.01] compared with wild-type. Further, pharmacologic disruption of TRPV1 with intrathecal resiniferatoxin, compared with vehicle, increased mortality risk [1.80 (1.05 to 3.2) hazard-ratio (95% confidence interval), p=0.03] in wild-type animals, but not in Trpv1-knock out mice. After lipopolysaccharide, neither genetic (Trpv1-knock out) nor pharmacologic disruption of TRPV1 with resiniferatoxin had significant effect on survival compared with respective controls. In contrast, after lipopolysaccharide, pharmacologic disruption of TRPV1 with capsazepine, compared with vehicle, increased mortality risk [1.92 (1.02 to 3.61) hazard-ratio (95% confidence interval), p=0.04] in wild-type animals. Further, after CLP, increased mortality in resiniferatoxin-treated-wild-type animals was associated with higher blood bacterial count (p=0.0004) and nitrate/nitrite levels and downregulation of tumor necrosis factor α expression (p=0.004) compared with controls. Genetic or pharmacologic disruption of TRPV1 can affect mortality, blood bacteria clearance, and cytokine response in sepsis in patterns that may vary according to the sepsis-inducing event and the method of TRPV1 disruption.
