Cold-inducible RNA-binding protein is an important mediator of alcohol-induced brain inflammation.
Cold-inducible RNA-binding protein is an important mediator of alcohol-induced brain inflammation.
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DOI：
10.1371/journal.pone.0079430
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Wang P
中科院分区：
文献类型：
--
作者：
Rajayer SR;Jacob A;Yang WL;Zhou M;Chaung W;Wang P
酗酒与脑功能障碍有关。乙醇诱导的小胶质细胞活化启动炎症过程，导致促炎细胞因子上调，这反过来又产生神经元炎症和损伤。然而，其分子机制尚未完全了解。我们推测，冷诱导RNA结合蛋白（CIRP），一种新的促炎分子，可以促进酒精诱导的神经炎症。为了验证这一理论，将雄性野生型（WT）小鼠暴露于与狂饮一致的浓度的酒精中，并收集血液和脑组织。在酒精后5 h，观察到CIRP mRNA在脑中的显著增加53%，并且其表达在10 h和15 h仍然升高。脑CIRP蛋白水平在10小时增加184%，并在15小时保持高水平。然后，我们将雄性WT和CIRP敲除（CIRP-/-）小鼠暴露于酒精，并在酒精输注后15小时收集血液和脑组织。组织损伤标志物（AST、ALT和LDH）的血清水平在暴露于酒精的WT小鼠中显著升高，而在CIRP−/−小鼠中升高较少。WT小鼠脑TNF-α mRNA和蛋白表达沿着IL-1β蛋白水平显著增加，而CIRP−/−小鼠中未观察到。在培养的BV 2细胞（小鼠小胶质细胞）中，100 mM乙醇在24 h和48 h分别显示CIRP mRNA增加274%和408%。还观察到TNF-α和IL-1β的相应增加。CIRP蛋白水平在培养基中显著增加，表明CIRP由BV 2细胞分泌。由此我们得出结论，酒精暴露激活小胶质细胞产生和分泌CIRP，并可能诱导促炎反应，从而引起神经炎症。CIRP可能是一种新的酒精性脑炎症介质。
Binge drinking has been associated with cerebral dysfunction. Ethanol induced microglial activation initiates an inflammatory process that causes upregulation of proinflammatory cytokines which in turn creates neuronal inflammation and damage. However, the molecular mechanism is not fully understood. We postulate that cold-inducible RNA-binding protein (CIRP), a novel proinflammatory molecule, can contribute to alcohol-induced neuroinflammation. To test this theory male wild-type (WT) mice were exposed to alcohol at concentrations consistent to binge drinking and blood and brain tissues were collected. At 5 h after alcohol, a significant increase of 53% in the brain of CIRP mRNA was observed and its expression remained elevated at 10 h and 15 h. Brain CIRP protein levels were increased by 184% at 10 h and remained high at 15 h. We then exposed male WT and CIRP knockout (CIRP−/−) mice to alcohol, and blood and brain tissues were collected at 15 h post-alcohol infusion. Serum levels of tissue injury markers (AST, ALT and LDH) were significantly elevated in alcohol-exposed WT mice while they were less increased in the CIRP−/− mice. Brain TNF-α mRNA and protein expressions along with IL-1β protein levels were significantly increased in WT mice, which was not seen in the CIRP−/− mice. In cultured BV2 cells (mouse microglia), ethanol at 100 mM showed an increase of CIRP mRNA by 274% and 408% at 24 h and 48 h respectively. Corresponding increases in TNF-α and IL-1β were also observed. CIRP protein levels were markedly increased in the medium, suggesting that CIRP was secreted by the BV2 cells. From this we conclude that alcohol exposure activates microglia to produce and secrete CIRP and possibly induce pro-inflammatory response and thereby causing neuroinflammation. CIRP could be a novel mediator of alcohol-induced brain inflammation.
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影响因子：
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