Salidroside attenuates inflammatory response via suppressing JAK2-STAT3 pathway activation and preventing STAT3 transfer into nucleus
Salidroside attenuates inflammatory response via suppressing JAK2-STAT3 pathway activation and preventing STAT3 transfer into nucleus
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红景天苷通过抑制 JAK2-STAT3 通路激活并阻止 STAT3 转移到细胞核来减轻炎症反应
DOI：
10.1016/j.intimp.2016.04.004
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发表时间：
2016-06-01
影响因子：
5.6
通讯作者：
Feng, Zunyong
中科院分区：
文献类型：
--
作者：
Qi, Zhilin;Qi, Shimei;Feng, Zunyong
红景天苷（Salidroside，SAL）是从红景天中分离得到的一种有效成分，具有较强的抗炎作用，但其作用机制尚不清楚。本研究旨在验证SAL对LPS诱导的炎症反应的影响，并探讨其可能的分子机制。将RAW264.7细胞与SAL预孵育2 h，然后用或不用LPS再刺激16 h。ELISA法检测TNF-α、MCP-1、IL-6和PGE 2的水平，亚硝酸盐分析法检测NO的产生。Western blotting检测一氧化氮合酶（iNOS）和环氧合酶-2（考克斯-2）的表达水平。在RAW264.7细胞和小鼠腹腔巨噬细胞中，信号分子的活化也通过Western印迹测量。激光共聚焦和核质分离实验检测STAT 3的核转位。结果表明，SAL剂量依赖性地抑制TNF-α、IL-6、MCP-1、PGE_2和NO的产生。SAL还能显著抑制LPS诱导的iNOS和考克斯-2的表达。进一步研究发现，SAL可下调LPS诱导的RAW 264. 7细胞和原代腹腔巨噬细胞JAK 2-STAT 3信号通路的磷酸化水平，减少STAT 3的核转位。此外，与体外实验结果一致，SAL能明显减少LPS诱导的小鼠急性肺损伤（ALI）模型中炎性细胞浸润，降低血清TNF-α和IL-6水平。综上所述，这些数据表明，SAL通过下调LPS诱导的JAX 2-STAT 3通路的激活并至少部分抑制STAT 3向核内的转移而发挥抗炎作用。(C)© 2016 Elsevier B. V.版权所有。
Salidroside (SAL) is an active ingredient isolated from the Rhodiola rosea, has potent anti-inflammatory effect, but the mechanism is still elusive. The purpose of this study is to verify the effects of SAL on LPS-induced inflammatory response and investigate the possible underlying molecular mechanism. RAW264.7 cells were pre incubated with SAL for 2 h, then stimulated with or without LPS for another 16 h. The levels of TNF-alpha, MCP-1, IL-6, and PGE2 were detected by ELISA, and the production of NO was determined by nitrite analysis. The expression levels of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were detected by Western blotting. In RAW264.7 cells and murine peritoneal macrophages, the activation of signal molecules was also measured by Western blot. The nuclear translocation of STAT3 was determined by Laser confocal and nucleocytoplasmic separation experiments. Our results showed that SAL attenuated the productions of TNF-alpha, IL-6, MCP-1, PGE2 and NO dose dependently. SAL also suppressed LPS-induced expressions of iNOS and COX-2 significantly. Further studies revealed that SAL down-regulated the phosphorylation of JAK2-STAT3 signaling pathway and reduced the nuclear translocation of STAT3 induced by LPS in RAW264.7 cells and primary peritoneal macrophages. In addition, consistent with the results in vitro, in the model of mice acute lung injury (ALI) induced by LPS, SAL reduced the infiltration of inflammatory cells and decreased the levels of serum TNF-alpha and IL-6 obviously. Taken together, these data indicated that SAL exerted anti-inflammatory action via down-regulating LPS-induced activation of JAX2-STAT3 pathway and suppressing STAT3 transfer into the nucleus at least in part. (C) 2016 Elsevier B.V. All rights reserved.