High Molecular Weight Hyaluronan Suppresses Macrophage M1 Polarization and Enhances IL-10 Production in PM2.5-Induced Lung Inflammation
High Molecular Weight Hyaluronan Suppresses Macrophage M1 Polarization and Enhances IL-10 Production in PM2.5-Induced Lung Inflammation
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高分子量透明质酸在 PM2.5 引起的肺部炎症中抑制巨噬细胞 M1 极化并增强 IL-10 的产生
DOI：
10.3390/molecules24091766
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发表时间：
2019-05-01
期刊：
影响因子：
4.6
通讯作者：
Zhao, Hang
中科院分区：
文献类型：
--
作者：
Shi, Qiwen;Zhao, Lan;Zhao, Hang
PM2.5是直径2.5m以下的颗粒物。气道巨噬细胞是调节 PM2.5 引起的炎症的关键角色。高分子量透明质酸 (HMW-HA) 先前已被证明对 PM2.5 引起的急性肺损伤和炎症具有保护作用。然而，人们对详细机制知之甚少。在本研究中，我们旨在确定 HMW-HA 是否通过调节巨噬细胞极化来减轻 PM2.5 诱导的肺部炎症。通过 ELISA、qPCR 和流式细胞术测量巨噬细胞产生的 M1 生物标志物 TNF-、IL-1、IL-6、CXCL1、CXCL2、NOS2 和 CD86 以及 M2 生物标志物 IL-10、MRC1 和 Arg-1 的水平。此外，通过CD68和NOS2的免疫荧光检查肺组织中M1巨噬细胞的数量。当同时施用 HMW-HA 时，我们观察到巨噬细胞和肺组织中 PM2.5 诱导的 M1 极化下降。同时，蛋白质印迹分析显示，PM2.5诱导的JNK和p38磷酸化被HMW-HA抑制。此外，体外和体内研究表明，HMW-HA和PM2.5的共刺激促进了IL-10的表达和释放，但对MRC1和ARG1的转录影响有限。总之，我们的结果表明，HMW-HA 通过 JNK 和 p38 途径抑制 M1 极化并促进促消退细胞因子 IL-10 的产生，从而改善 PM2.5 诱导的肺部炎症。
PM2.5 is particulate matter with a diameter of 2.5 m or less. Airway macrophages are the key players regulating PM2.5-induced inflammation. High molecular weight hyaluronan (HMW-HA) has previously been shown to exert protective effects on PM2.5-induced acute lung injury and inflammation. However, little is known about the detailed mechanism. In this study, we aimed to determine whether HMW-HA alleviates PM2.5-induced pulmonary inflammation by modulating macrophage polarization. The levels of M1 biomarkers TNF-, IL-1, IL-6, CXCL1, CXCL2, NOS2 and CD86, as well as M2 biomarkers IL-10, MRC1, and Arg-1 produced by macrophages were measured by ELISA, qPCR, and flow cytometry. In addition, the amount of M1 macrophages in lung tissues was examined by immunofluorescence of CD68 and NOS2. We observed a decline in PM2.5-induced M1 polarization both in macrophages and lung tissues when HMW-HA was administered simultaneously. Meanwhile, western blot analysis revealed that PM2.5-induced JNK and p38 phosphorylation was suppressed by HMW-HA. Furthermore, in vitro and in vivo studies showed that co-stimulation with HMW-HA and PM2.5 promoted the expression and release of IL-10, but exhibited limited effects on the transcription of MRC1 and ARG1. In conclusion, our results demonstrated that HMW-HA ameliorates PM2.5-induced lung inflammation by repressing M1 polarization through JNK and p38 pathways and promoting the production of pro-resolving cytokine IL-10.