High mobility group box 1/Toll-like receptor danger signaling increases brain neuroimmune activation in alcohol dependence.
High mobility group box 1/Toll-like receptor danger signaling increases brain neuroimmune activation in alcohol dependence.
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DOI：
10.1016/j.biopsych.2012.09.030
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发表时间：
2013-04-01
影响因子：
10.6
通讯作者：
Zou, Jian
中科院分区：
文献类型：
--
作者：
Crews, Fulton T.;Qin, Liya;Sheedy, Donna;Vetreno, Ryan P.;Zou, Jian
先天免疫基因的表达部分通过高迁移率族蛋白1(HMGB1)调节，HMGB1是一种内源性促炎细胞因子，激活与危险信号相关的白细胞介素1/Toll样受体(IL-1/TLR)家族的多个成员。我们研究了HMGB1、TLR2、TLR3和TLR4在慢性乙醇处理的小鼠脑、死后人酒精脑和大鼠脑切片培养中的表达，以验证酒精脑中神经免疫激活涉及乙醇激活HMGB1/TLR危险信号的假说。用Western印迹、ELISA法、免疫组织化学(+IR)和实时定量聚合酶链式反应(RT-PCR)检测酒精处理小鼠(5g/kg/d，10天+24小时)、大鼠脑片培养和死后人酒精脑组织中的蛋白水平和mRNA水平。乙醇处理增加了小鼠脑内HMGB1、TLR2、TLR3和TLR4的mRNA和+IR蛋白的表达。死后的人类酒精脑还显示HMGB1、TLR2、TLR3和TLR4+IR细胞增加，这些细胞与终生饮酒以及彼此相关。乙醇处理的脑片培养上清液中释放HMGB1，诱导促炎细胞因子IL-1β的产生。抗HMGB1的中和抗体和抗HMGB1或TLR4的小分子抑制基因可钝化乙醇诱导的IL-1β。乙醇诱导的HMGB1/TLR信号转导有助于促炎细胞因子IL-1β的诱导。HMGB1、TLR2、TLR3和TLR4在酒精和乙醇处理的小鼠脑中的表达增加，表明慢性酒精诱导的脑神经免疫激活是通过HMGB1/TLR信号转导发生的。
Innate immune gene expression is regulated in part through high mobility group box 1(HMGB1), an endogenous proinflammatory cytokine, that activates multiple members of the interleukin-1/Toll-like receptor (IL-1/TLR) family associated with danger signaling. We investigated expression of HMGB1, TLR2, TLR3 and TLR4 in chronic ethanol treated mouse brain, post-mortem human alcoholic brain, and rat brain slice culture to test the hypothesis that neuroimmune activation in alcoholic brain involves ethanol activation of HMGB1/TLR danger signaling. Protein levels were assessed using Western blot, ELISA, immunohistochemical immunoreactivity (+IR), and mRNA levels were measured by real time PCR in ethanol-treated mice (5 g/kg/day, i.g., 10 days + 24 hr), rat brain slice culture, and post-mortem human alcoholic brain. Ethanol treatment of mice increased brain mRNA and +IR protein expression of HMGB1, TLR2, TLR3, and TLR4. Post-mortem human alcoholic brain also showed increased HMGB1, TLR2, TLR3, and TLR4+IR cells that correlated with lifetime alcohol consumption as well as each other. Ethanol treatment of brain slice culture released HMGB1 into the media and induced the proinflammatory cytokine, IL-1β. Neutralizing antibodies to HMGB1 and small inhibitory mRNA to HMGB1 or TLR4 blunted ethanol induction of IL-1β. Ethanol-induced HMGB1/TLR signaling contributes to induction of the proinflammatory cytokine, IL-1β. Increased expression of HMGB1, TLR2, TLR3, and TLR4 in alcoholic brain and in mice treated with ethanol suggests that chronic alcohol-induced brain neuroimmune activation occurs through HMGB1/TLR signaling.
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影响因子：
3.6
作者：
Crews, Fulton Timm;Boettiger, Charlotte Ann
通讯作者：
Boettiger, Charlotte Ann
影响因子：
9.3
作者：
Feldman P;Due MR;Ripsch MS;Khanna R;White FA
通讯作者：
White FA
影响因子：
5.3
作者：
Alfonso-Loeches, Silvia;Pascual-Lucas, Maya;Guerri, Consuelo
通讯作者：
Guerri, Consuelo
DOI：
10.1111/j.1530-0277.1996.tb01055.x
发表时间：
1996-02-01
影响因子：
3.2
作者：
Carson, EJ;Pruett, SB
通讯作者：
Pruett, SB
影响因子：
15.1
作者：
Crews, F. T.;Zou, Jian;Qin, Liya
通讯作者：
Qin, Liya