Insulin Antagonizes LPS-Induced Inflammatory Responses by Activating SR-A1/ERK Axis in Macrophages
Insulin Antagonizes LPS-Induced Inflammatory Responses by Activating SR-A1/ERK Axis in Macrophages
复制标题
胰岛素通过激活巨噬细胞中的 SR-A1/ERK 轴来拮抗 LPS 诱导的炎症反应
DOI：
10.1007/s10753-018-0933-1
复制
发表时间：
2019
期刊：
影响因子：
5.1
通讯作者：
Chen Qi
中科院分区：
文献类型：
--
作者：
Zhu Liu;Fan Lei;Zhu Yaqin;Wang Yan;Bai Hui;Yang Qing;Ben Jingjing;Zhang Hanwen;Li Xiaoyu;Zhu Xudong;Chen Qi
摘要胰岛素是机体代谢和炎症的重要调节因子。然而，胰岛素抗炎作用的机制尚未完全清楚。在本研究中，我们研究了A1类清道夫受体（SR-A1），模式识别受体家族的原型成员，在胰岛素介导的巨噬细胞炎症反应的抑制中的作用。我们的小鼠体内研究表明，胰岛素可以以SR-A1依赖的方式减轻脂多糖（LPS）诱导的内毒素血症，这与我们的体外研究结果一致，即SR-A1是胰岛素拮抗LPS诱导的巨噬细胞炎症反应所必需的。SR-A1对胰岛素抗炎作用的影响可能与其激活巨噬细胞的细胞外信号调节激酶（ERK）信号通路有关。胰岛素可以通过SR-A1/ERK级联反应抑制巨噬细胞极化为促炎表型。总的来说，我们的研究结果表明，SR-A1可能是胰岛素在巨噬细胞中抗炎作用的关键因素。
AbstractInsulin is a key regulator of metabolism and inflammation in the body. However, the mechanism of the anti-inflammatory effect of insulin is not fully understood. In the present study, we investigated the role of the class A1 scavenger receptor (SR-A1), a prototypic member of the pattern recognition receptor family, in the insulin-mediated suppression of inflammatory responses in macrophages. Our murinein vivostudies show that insulin can attenuate lipopolysaccharide (LPS)-induced endotoxemia in a SR-A1-dependent manner, and this was consistent with ourin vitroresults which demonstrate that the SR-A1 is necessary for insulin to antagonize the LPS-induced inflammatory responses in macrophages. The effect of SR-A1 on the anti-inflammatory action of insulin might be associated with the activation of the extracellular signal-regulated kinases (ERK) signaling pathway in macrophages. Insulin could inhibit macrophage polarization to a pro-inflammatory phenotypeviathe SR-A1/ERK cascade. Collectively, our results suggest that SR-A1 may be a pivotal element for the anti-inflammation effect of insulin in macrophages.