Protein Disulfide Isomerase Silence Inhibits Inflammatory Functions of Macrophages by Suppressing Reactive Oxygen Species and NF-kappa B Pathway
Protein Disulfide Isomerase Silence Inhibits Inflammatory Functions of Macrophages by Suppressing Reactive Oxygen Species and NF-kappa B Pathway
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蛋白质二硫键异构酶沉默通过抑制活性氧和 NF-κ B 通路来抑制巨噬细胞的炎症功能
DOI：
10.1007/s10753-017-0717-z
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发表时间：
2018
期刊：
影响因子：
5.1
通讯作者：
Sheng Puyi
中科院分区：
文献类型：
--
作者：
Xiao Yinbo;Li Chaohong;Gu Minghui;Wang Haixing;Chen Weishen;Luo Guotian;Yang Guangpu;Zhang Ziji;Zhang Yangchun;Xian Guoyan;Li Ziqing;Sheng Puyi
摘要巨噬细胞在炎症反应中起重要作用。蛋白质二硫键异构酶（PDI）是氧化还原系统的核心，与巨噬细胞的炎症功能密切相关。然而，PDI与炎症之间的关系仍然未知。在这项研究中，我们测试了PDI对脂多糖（LPS）刺激的RAW 264.7巨噬细胞中炎症反应的影响。使用CRISPR/Cas9系统，我们发现PDI敲除抑制迁移、M1极化以及肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）的分泌。这些炎症过程的抑制伴随着活性氧（ROS）的产生减少。PDI消融还灭活了激活的B细胞（NF-κB）的核因子κ轻链增强子的磷酸化，并激活了NF-κB抑制剂α（IκBα）的磷酸化。这些发现表明PDI敲除通过减少ROS产生和失活NF-κB通路来抑制巨噬细胞的炎症功能。
AbstractMacrophages play an essential role in inflammation. Protein disulfide isomerase (PDI) is central to the redox system, which is closely linked with the inflammatory function of macrophages. However, the relationship between PDI and inflammation is still unknown. In this study, we tested the effects of PDI on inflammatory responses in RAW 264.7 macrophages stimulated with lipopolysaccharide (LPS). Using CRISPR/Cas9 system, we found that PDI knockout suppressed migration, M1 polarization, and secretion of tumor necrosis factor-α (TNF-α) and interluekin-6 (IL-6). The repression of these inflammatory processes was accompanied by decreased production of reactive oxygen species (ROS). PDI ablation also inactivated the phosphorylation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and activated the phosphorylation of NF-κB inhibitor alpha (IκBα). These findings demonstrate that PDI knockout inhibits the inflammatory function of macrophages by decreasing ROS production and inactivating NF-κB pathway.