HMGB1 binding to receptor for advanced glycation end products enhances inflammatory responses of human bronchial epithelial cells by activating p38 MAPK and ERK1/2
HMGB1 binding to receptor for advanced glycation end products enhances inflammatory responses of human bronchial epithelial cells by activating p38 MAPK and ERK1/2
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DOI：
10.1007/s11010-015-2396-0
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发表时间：
2015-07-01
影响因子：
4.3
通讯作者：
Chen, Yiqiang
中科院分区：
文献类型：
--
作者：
Liang, Yue;Hou, Changchun;Chen, Yiqiang
促炎因子高迁移率族蛋白1（HMGB 1）已被认为是许多慢性炎症性疾病（包括哮喘）的重要介质。人支气管上皮细胞（HBECs）在哮喘的发病机制中起着重要作用。然而，HMGB 1对HBEC的影响及其机制尚不清楚。在这里，我们研究了受体表达和促炎细胞因子的产生由原代培养的HBECs刺激HMGB 1。然后，我们研究了特异性受体阻断和抑制p38 MAPK，ERK 1/2，或PI 3-K对HMGB 1诱导的促炎细胞因子表达的影响。HMGB 1以剂量和时间依赖性方式增加TNF-α、TSLP、MMP-9和VEGF的表达和分泌。HMGB 1还诱导了HMGB 1蛋白的表达升高。TNF-α、VEGF、MMP-9和TSLP的分泌显著降低，而ERK 1/2抑制介导的效应不太明显。这些观察结果表明，HMGB 1结合HBECs的p38 MAPK和ERK 1/2途径，并促进活动。然后，这增强了TNF-α、VEGF、MMP-9和TSLP的表达，这些是哮喘中的重要炎症因子。这些结果表明，HMGB 1增强了HBEC的炎症反应，这参与了哮喘炎症过程的调节。
The proinflammatory factor high mobility group box protein 1 (HMGB1) has been implicated as an important mediator of many chronic inflammatory diseases, including asthma. Human bronchial epithelial cells (HBECs) play a central role in the pathogenesis of asthma. However, the effects of HMGB1 on HBECs and the underlying mechanisms remain unknown. Here, we investigated receptor expression and proinflammatory cytokine production by primary cultures of HBECs stimulated by HMGB1. We then examined the effects of specific receptor blockade and inhibition of p38 MAPK, ERK1/2, or PI3-K on HMGB1-induced expression of proinflammatory cytokines. HMGB1 increased the expression and secretion of TNF-alpha, TSLP, MMP-9, and VEGF in a dose-and time-dependent manner. HMGB1 also induced elevated expression of RAGE protein. Secretion of TNF-alpha, VEGF, MMP-9, and TSLP was significantly decreased by RAGE blockade and p38 MAPK pathway inhibition, while a less pronounced effect was mediated by ERK1/2 inhibition. These observations suggest that HMGB1 binds RAGE and promotes activities of p38 MAPK and ERK1/2 pathways in HBECs. This then enhances the expression of TNF-alpha, VEGF, MMP-9, and TSLP, which are the important inflammatory factors in asthma. These results demonstrate that HMGB1 enhances the inflammatory responses of HBECs, which are involved in the modulation of inflammatory processes in asthma.