Intestinal Epithelium-Derived Luminally Released Extracellular Vesicles in Sepsis Exhibit the Ability to Suppress TNF-a and IL-17A Expression in Mucosal Inflammation.
Intestinal Epithelium-Derived Luminally Released Extracellular Vesicles in Sepsis Exhibit the Ability to Suppress TNF-a and IL-17A Expression in Mucosal Inflammation.
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DOI：
10.3390/ijms21228445
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发表时间：
2020-11-10
影响因子：
5.6
通讯作者：
Shimaoka M
中科院分区：
文献类型：
--
作者：
Appiah MG;Park EJ;Darkwah S;Kawamoto E;Akama Y;Gaowa A;Kalsan M;Ahmad S;Shimaoka M
脓毒症是一种全身性炎症性疾病，由对感染的免疫反应失调引起，导致包括肠道在内的多个关键器官功能障碍。先前的研究报告了脓毒症小鼠和患者血液中循环的外泌体促进或抑制炎症的能力的对比结果。关于脓毒症期间肠腔内释放的肠上皮细胞衍生的外泌体如何影响粘膜炎症，人们知之甚少。为了研究这个问题，我们从脓毒症小鼠的肠道灌洗液中分离出细胞外囊泡（EV）。 EVs表达典型的外泌体（CD63和CD9）和上皮细胞（EpCAM）标记物，脓毒症时这些标记物进一步增加。此外，将脓毒症-EV注射到发炎的肠道中会导致促炎细胞因子TNF-α和IL-17A的信号传导显着减少。 MicroRNA (miRNA) 分析以及逆转录和定量聚合酶链反应 (RT-qPCR) 显示脓毒症诱导的多种 miRNA 外泌体增加，这些 miRNA 可能靶向 TNF-α 和 IL-17A。这些结果意味着肠上皮细胞 (IEC) 衍生的管腔 EV 携带可减轻促炎症反应的 miRNA。总而言之，我们的研究提出了一种新机制，脓毒症期间释放的 IEC EV 将调节性 miRNA 转移到细胞中，可能有助于改善肠道炎症。
Sepsis is a systemic inflammatory disorder induced by a dysregulated immune response to infection resulting in dysfunction of multiple critical organs, including the intestines. Previous studies have reported contrasting results regarding the abilities of exosomes circulating in the blood of sepsis mice and patients to either promote or suppress inflammation. Little is known about how the gut epithelial cell-derived exosomes released in the intestinal luminal space during sepsis affect mucosal inflammation. To study this question, we isolated extracellular vesicles (EVs) from intestinal lavage of septic mice. The EVs expressed typical exosomal (CD63 and CD9) and epithelial (EpCAM) markers, which were further increased by sepsis. Moreover, septic-EV injection into inflamed gut induced a significant reduction in the messaging of pro-inflammatory cytokines TNF-α and IL-17A. MicroRNA (miRNA) profiling and reverse transcription and quantitative polymerase chain reaction (RT-qPCR) revealed a sepsis-induced exosomal increase in multiple miRNAs, which putatively target TNF-α and IL-17A. These results imply that intestinal epithelial cell (IEC)-derived luminal EVs carry miRNAs that mitigate pro-inflammatory responses. Taken together, our study proposes a novel mechanism by which IEC EVs released during sepsis transfer regulatory miRNAs to cells, possibly contributing to the amelioration of gut inflammation.
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DOI：
10.1016/j.surge.2012.03.003
发表时间：
2012-12
影响因子：
2.5
作者：
Deitch, Edwin A.
通讯作者：
Deitch, Edwin A.
影响因子：
16
作者：
Crescitelli R;Lässer C;Szabó TG;Kittel A;Eldh M;Dianzani I;Buzás EI;Lötvall J
通讯作者：
Lötvall J
DOI：
10.4049/jimmunol.1203170
发表时间：
2013-04-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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作者：
Deng ZB;Zhuang X;Ju S;Xiang X;Mu J;Liu Y;Jiang H;Zhang L;Mobley J;McClain C;Feng W;Grizzle W;Yan J;Miller D;Kronenberg M;Zhang HG
通讯作者：
Zhang HG
影响因子：
46.9
作者：
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影响因子：
3.7
作者：
Duong, Phat;Chung, Allen;Raffai, Robert L.
通讯作者：
Raffai, Robert L.