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iTRAQ 分析细胞外囊泡揭示:SiO 通过激活 NOD-RIP2-NF-κB 信号通路诱导 RAW264.7 巨噬细胞极化。

iTRAQ-based secretome reveals that SiO induces the polarization of RAW264.7 macrophages by activation of the NOD-RIP2-NF-κB signaling pathway.

机构信息

Central Laboratory, Logistics University of Chinese People's Armed Police Force, Tianjin City 300162, China; Xinxiang Medical University, School of Public Health, Xinxiang 453003, China.

Logistics University of Chinese People's Armed Police Forces, Tianjin 300162, China.

出版信息

Environ Toxicol Pharmacol. 2018 Oct;63:92-102. doi: 10.1016/j.etap.2018.08.010. Epub 2018 Aug 17.

DOI:10.1016/j.etap.2018.08.010
PMID:30189374
Abstract

Silicosis is characterized by inflammation and pulmonary fibrosis due to long-term inhalation of crystalline silica (SiO). To clarify the role of macrophage polarization in the inflammatory response of silicosis, we used iTRAQ-coupled 2D LC-MS/MS to study the change in the secretome in RAW264.7 macrophages. We successfully screened 330 differentially expressed proteins, including 120 proteins with upregulated expression and 210 proteins with down-regulated expression (p < 0.05). Bioinformatics analysis showed that the differentially expressed proteins were mainly involved in biological processes, such as oxidative stress, mitochondrial damage, apoptosis and acute inflammatory response. In particular, the expression levels of mitochondrial apoptosis-related proteins, such as AKT1, BAX, HSPD1, TNF, CASP8 and DAP, were increased after SiO exposure. Taken together, our study indicated that SiO could induce macrophage polarization by activation of the NOD-RIP2-NF-κB signaling pathway in RAW264.7 macrophages. This may represent a potential mechanism in the development of silicosis.

摘要

硅肺的特征是由于长期吸入结晶二氧化硅(SiO)而引起的炎症和肺纤维化。为了阐明巨噬细胞极化在矽肺炎症反应中的作用,我们使用 iTRAQ 耦联二维 LC-MS/MS 研究 RAW264.7 巨噬细胞中分泌组的变化。我们成功筛选出 330 个差异表达蛋白,其中 120 个蛋白表达上调,210 个蛋白表达下调(p < 0.05)。生物信息学分析表明,差异表达蛋白主要参与生物学过程,如氧化应激、线粒体损伤、细胞凋亡和急性炎症反应。特别是,SiO 暴露后,线粒体凋亡相关蛋白 AKT1、BAX、HSPD1、TNF、CASP8 和 DAP 的表达水平增加。综上所述,我们的研究表明,SiO 可能通过激活 RAW264.7 巨噬细胞中的 NOD-RIP2-NF-κB 信号通路诱导巨噬细胞极化。这可能代表了矽肺发生的潜在机制。

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