Exosomes derived from mature dendritic cells increase endothelial inflammation and atherosclerosis via membrane TNF-α mediated NF-κB pathway.
Exosomes derived from mature dendritic cells increase endothelial inflammation and atherosclerosis via membrane TNF-α mediated NF-κB pathway.
复制标题
来自成熟树突状细胞的外泌体通过膜 TNF-α 介导的 NF-κ B 途径增加内皮炎症和动脉粥样硬化
DOI：
10.1111/jcmm.12923
复制
发表时间：
2016-12
影响因子：
5.3
通讯作者：
Ge J
中科院分区：
文献类型：
--
作者：
Gao W;Liu H;Yuan J;Wu C;Huang D;Ma Y;Zhu J;Ma L;Guo J;Shi H;Zou Y;Ge J
树突状细胞（DC）衍生的外泌体是否在内皮炎症和动脉粥样硬化的进展中发挥作用仍不清楚。使用transwell系统和exosome释放抑制剂GW 4869，我们证明了成熟DC有助于内皮炎症，并且exosome参与了该过程。为了进一步证实这一发现，我们从骨髓树突状细胞（BMDC）培养基中分离外泌体（命名为DC-exos），并用这些DC-exos刺激人脐静脉内皮细胞（HUVEC）。我们观察到成熟的DC‐exos通过NF-κB途径以类似于脂多糖的方式增加HUVEC炎症。在对外泌体进行蛋白质阵列分析后，我们鉴定并证实了外泌体膜上的肿瘤坏死因子（TNF）-α是HUVECs中NF-κB通路的触发因子。然后我们进行了体内研究，发现小鼠的主动脉内皮可以摄取静脉注射的exosomes，并被这些exosomes激活。在将成熟DC‐exos注射到ApoE−/−小鼠中12周后，动脉粥样硬化病变显著增加。我们的研究表明，成熟DC来源的外泌体通过膜TNF-α介导的NF-κB途径增加内皮炎症和动脉粥样硬化。这一发现扩展了我们对DCs如何影响炎症的认识，并提供了一种预防内皮炎症和动脉粥样硬化的潜在方法。
Whether dendritic cell (DC) derived exosomes play a role in the progression of endothelial inflammation and atherosclerosis remains unclear. Using a transwell system and exosome release inhibitor GW4869, we demonstrated that mature DCs contributed to endothelial inflammation and exosomes were involved in the process. To further confirm this finding, we isolated exosomes from bone marrow dendritic cell (BMDC) culture medium (named DC‐exos) and stimulated human umbilical vein endothelial cell (HUVEC) with these DC‐exos. We observed that mature DC‐exos increased HUVEC inflammation through NF‐κB pathway in a manner similar to that of lipopolysaccharide. After a protein array analysis of exosomes, we identified and confirmed tumour necrosis factor (TNF)‐α on exosome membrane being the trigger of NF‐κB pathway in HUVECs. We then performed an in vivo study and found that the aorta endothelial of mice could uptake intravenously injected exosomes and was activated by these exosomes. After a period of 12 weeks of mature DC‐exos injection into ApoE−/− mice, the atherosclerotic lesions significantly increased. Our study demonstrates that mature DCs derived exosomes increase endothelial inflammation and atherosclerosis via membrane TNF‐α mediated NF‐κB pathway. This finding extends our knowledge on how DCs affect inflammation and provides a potential method to prevent endothelial inflammation and atherosclerosis.
登录
查看更多内容
影响因子：
16.8
作者：
Koltsova EK;Ley K
通讯作者：
Ley K
影响因子：
3.5
作者：
Laulagnier, K;Grand, D;Record, M
通讯作者：
Record, M
microRNA-181a 通过靶向 c-Fos 抑制树突状细胞中 ox-LDL 刺激的炎症反应
影响因子：
6.5
作者：
Wu C;Gong Y;Yuan J;Zhang W;Zhao G;Li H;Sun A;KaiHu;Zou Y;Ge J
通讯作者：
Ge J
影响因子：
4.2
作者：
Dinkins MB;Dasgupta S;Wang G;Zhu G;Bieberich E
通讯作者：
Bieberich E
DOI：
10.1073/pnas.1209414109
发表时间：
2012-07-31
影响因子：
11.1
作者：
Fabbri, Muller;Paone, Alessio;Croce, Carlo M.
通讯作者：
Croce, Carlo M.