Inflammasome-Derived Exosomes Activate NF-κB Signaling in Macrophages.
Inflammasome-Derived Exosomes Activate NF-κB Signaling in Macrophages.
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DOI：
10.1021/acs.jproteome.6b00599
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发表时间：
2017-01
影响因子：
4.4
通讯作者：
Yuehui Zhang;Fangbing Liu;Yanzhi Yuan;Chaozhi Jin;Cheng Chang;Yun-ping Zhu;Xiuyuan Zhang;Chunyan Tian;F. He;Jian Wang
中科院分区：
文献类型：
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作者：
Yuehui Zhang;Fangbing Liu;Yanzhi Yuan;Chaozhi Jin;Cheng Chang;Yun-ping Zhu;Xiuyuan Zhang;Chunyan Tian;F. He;Jian Wang
外泌体是分泌的小泡，介导多种生物过程，如肿瘤发生和免疫反应。然而，炎性小体信号是否导致外泌体成分的改变及其在免疫应答中的作用仍有待确定。我们用假体、内毒素或内毒素/尼日利亚菌素处理巨噬细胞分离外泌体。采用MS/MS无标记定量方法鉴定外泌体成分。在内毒素和尼日利亚菌素处理的外泌体中，共鉴定出2331种蛋白，其中513种蛋白被特异性检测到。通过Gene Ontology和KEGG途径对差异表达蛋白进行分类。免疫反应相关蛋白和信号通路在炎性小体衍生的外泌体中特异性富集。此外，我们用不同刺激的外泌体处理巨噬细胞。我们发现炎性小体来源的外泌体直接激活NF-κB信号通路，而对照或内毒素来源的外泌体没有作用。炎症信号以依赖外泌体的方式在邻近细胞中被放大。炎性小体衍生的外泌体可能用于增强疾病治疗中的免疫反应，防止这些外泌体的转移可能改善自身免疫性疾病。
Exosomes are secreted small vesicles that mediate various biological processes, such as tumorigenesis and immune response. However, whether the inflammasome signaling leads to the change of constituent of exosomes and its roles in immune response remains to be determined. We isolated the exosomes from macrophages with treatment of mock, endotoxin, or endotoxin/nigericin. A label-free quantification method by MS/MS was used to identify the components of exosomes. In total, 2331 proteins were identified and 513 proteins were exclusively detected in exosomes with endotoxin and nigericin treatment. The differentially expressed proteins were classified by Gene Ontology and KEGG pathways. The immune response-related proteins and signaling pathways were specifically enriched in inflammasome-derived exosomes. Moreover, we treated macrophages with the exosomes from different stimulation. We found that inflammasome-derived exosomes directly activate NF-κB signaling pathway, while the control or endotoxin-derived exosomes have no effect. The inflammatory signaling was amplified in neighbor cells in an exosome-dependent way. The inflammasome-derived exosomes might be used to augment the immune response in disease treatment, and preventing the transfer of these exosomes might ameliorate autoimmune diseases.