Preconditioning of physiological cyclic stretch attenuated HMGB1 expression in pathologically mechanical stretch-activated A549 cells and ventilator-induced lung injury rats through inhibition of IL-6/STAT3/SOCS3
Preconditioning of physiological cyclic stretch attenuated HMGB1 expression in pathologically mechanical stretch-activated A549 cells and ventilator-induced lung injury rats through inhibition of IL-6/STAT3/SOCS3
复制标题
生理循环拉伸的预处理通过抑制 IL-6/STAT3/SOCS3 减弱了病理机械拉伸激活的 A549 细胞和呼吸机诱导的肺损伤大鼠中 HMGB1 的表达。
DOI：
10.1016/j.intimp.2015.12.017
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发表时间：
2016-02-01
影响因子：
5.6
通讯作者：
Gao, Ju
中科院分区：
文献类型：
--
作者：
Fang, Xiang-Zhi;Huang, Tian-Feng;Gao, Ju
先前的研究表明，生理循环拉伸（5% CS）通过STAT3减弱氧化和脂多糖诱导的HMGB1表达的增加。然而，在呼吸机肺损伤（VILI）中起关键作用的hmgb1在生理周期拉伸（CS）的前提条件下对其表达的影响知之甚少。我们发现5% cs预处理显著抑制HMGB 1表达，但对HMGB 1受体没有抑制作用。5% cs预处理对IL-6/STAT3通路有抑制作用，而5% cs预处理对hmgb1表达的抑制作用通过额外处理rmlL-6而被消除。5% cs预处理也能诱导SOCS3上调，5% cs预处理不能抑制转染SOCS3 siRNA的细胞中的IL-6/STAT3通路。此外，低潮气量通气预处理也降低了VILI的严重程度，这可以从肺泡-毛细血管屏障功能障碍、湿/干重比和组织学分析的显著改善中得到证明。上述结果表明，生理5% CS预处理可通过上调SOCS3表达的IL-6/STAT3通路，降低病理性机械拉伸诱导的hmgb1表达。(C) 2015 Elsevier B.V.版权所有
Previous studies have shown that physiologically cyclic stretch (5% CS) attenuated both oxidative- and LPS-induced increases in HMGB1 expression via STAT3. However, little information exists about the effect of precondition of physiological cyclic stretch (CS) on the expression of HMGB 1, which play a crucial role in ventilator induced lung injury (VILI). We found that 5% CS-preconditioning significantly inhibited HMGB 1 expression, but not HMGB 1 receptors. 5% CS-preconditioning inhibits the IL-6/STAT3 pathway, and the inhibitory effect on the expression of HMGB 1 induced by 5% CS-preconditioning is abolished by additional treatment of rmlL-6. 5% CS-preconditioning also induces SOCS3 upregulation, and 5% CS-preconditioning fails to inhibit the IL-6/STAT3 pathway in cells transfected with SOCS3 siRNA. Moreover, low tidal volume ventilation preconditioning also decreases the severity of VILI evidenced by the markedly improved pulmonary alveolar-capillary barrier dysfunction, wet/dry weight ratio, and histological analysis. These results suggest that preconditioning of physiological 5% CS can reduce the expression of HMGB 1 induced by pathologically mechanical stretch through IL-6/STAT3 pathway associated with up-regulated SOCS3 expression. (C) 2015 Elsevier B.V. All rights reserved.