Heat shock preconditioning mesenchymal stem cells attenuate acute lung injury via reducing NLRP3 inflammasome activation in macrophages.
Heat shock preconditioning mesenchymal stem cells attenuate acute lung injury via reducing NLRP3 inflammasome activation in macrophages.
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热休克预处理间充质干细胞通过减少巨噬细胞中NLRP3炎症小体的激活来减轻急性肺损伤
DOI：
10.1186/s13287-021-02328-3
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发表时间：
2021-05-17
影响因子：
7.5
通讯作者：
Yi H
中科院分区：
文献类型：
--
作者：
Lv H;Yuan X;Zhang J;Lu T;Yao J;Zheng J;Cai J;Xiao J;Chen H;Xie S;Ruan Y;An Y;Sui X;Yi H
急性肺损伤（ALI）仍然是全世界发病和死亡的常见原因，迄今为止，ALI 尚无有效的治疗方法。先前的研究表明，局部施用间充质干细胞（MSC）可以减轻实验性急性肺损伤的病理变化。热休克（HS）预处理已被确定为增强细胞存活和功能的方法。本研究旨在评估 HS 预处理的 MSC 是否可以增强免疫调节和 ALI 的恢复。 HS预处理42℃1h，检测生物学特性和分泌功能的变化。在ALI小鼠体内模型中，我们鼻内给予预处理的脐带源性间充质干细胞（UC-MSCs），证实其治疗效果，并检测支气管肺泡灌洗液（BALF）中巨噬细胞的表型。为了阐明其潜在机制，我们在体外将预处理的UC-MSCs与巨噬细胞共培养，并评估了巨噬细胞中炎性体相关蛋白的表达水平。数据显示，HS预处理后，UC-MSCs的活力或生物学特性没有表现出显着的变化。 HS预处理的UC-MSCs给予ALI模型可改善病理变化和肺损伤相关指标，降低促炎细胞因子水平，调节M1/M2巨噬细胞平衡。从机制上讲，体内和体外研究均表明 HS 预处理增强了 UC-MSC 中 HSP70 的蛋白水平，从而负向调节肺泡巨噬细胞中 NLR 家族 Pyrin 结构域 3 (NLRP3) 炎症小体的激活。通过敲除 HSP70 表达，这些效应部分逆转。 HS预处理可以增强UC-MSC在ALI期间抑制巨噬细胞NLRP3炎性体激活的有益作用。其机制可能与HSP70表达上调有关。在线版本包含可在 10.1186/s13287-021-02328-3 获取的补充材料。
Acute lung injury (ALI) remains a common cause of morbidity and mortality worldwide, and to date, there is no effective treatment for ALI. Previous studies have revealed that topical administration of mesenchymal stem cells (MSCs) can attenuate the pathological changes in experimental acute lung injury. Heat shock (HS) pretreatment has been identified as a method to enhance the survival and function of cells. The present study aimed to assess whether HS-pretreated MSCs could enhance immunomodulation and recovery from ALI. HS pretreatment was performed at 42 °C for 1 h, and changes in biological characteristics and secretion functions were detected. In an in vivo mouse model of ALI, we intranasally administered pretreated umbilical cord-derived MSCs (UC-MSCs), confirmed their therapeutic effects, and detected the phenotypes of the macrophages in bronchoalveolar lavage fluid (BALF). To elucidate the underlying mechanisms, we cocultured pretreated UC-MSCs with macrophages in vitro, and the expression levels of inflammasome-related proteins in the macrophages were assessed. The data showed that UC-MSCs did not exhibit significant changes in viability or biological characteristics after HS pretreatment. The administration of HS-pretreated UC-MSCs to the ALI model improved the pathological changes and lung damage-related indexes, reduced the proinflammatory cytokine levels, and modulated the M1/M2 macrophage balance. Mechanistically, both the in vivo and in vitro studies demonstrated that HS pretreatment enhanced the protein level of HSP70 in UC-MSCs, which negatively modulated NLR family pyrin domain containing 3 (NLRP3) inflammasome activation in alveolar macrophages. These effects were partially reversed by knocking down HSP70 expression. HS pretreatment can enhance the beneficial effects of UC-MSCs in inhibiting NLRP3 inflammasome activation in macrophages during ALI. The mechanism may be related to the upregulated expression of HSP70. The online version contains supplementary material available at 10.1186/s13287-021-02328-3.
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影响因子：
16.6
作者：
Liu C;Lou W;Yang JC;Liu L;Armstrong CM;Lombard AP;Zhao R;Noel ODV;Tepper CG;Chen HW;Dall'Era M;Evans CP;Gao AC
通讯作者：
Gao AC
DOI：
10.1164/rccm.201701-0170oc
发表时间：
2017-11-15
影响因子：
24.7
作者：
Morrison, Thomas J.;Jackson, Megan V.;Krasnodembskaya, Anna D.
通讯作者：
Krasnodembskaya, Anna D.
影响因子：
2.6
作者：
Gao, Feng;Hu, Xinyang;Wang, Jianan
通讯作者：
Wang, Jianan
间充质干细胞通过抑制中性粒细胞募集改善肝脏缺血/再灌注损伤
影响因子：
4.1
作者：
Li, Shihui;Zheng, Xu;Yang, Yang
通讯作者：
Yang, Yang
DOI：
10.1073/pnas.1614935113
发表时间：
2016-12-13
影响因子：
11.1
作者：
Mittal, Manish;Tiruppathi, Chinnaswamy;Malik, Asrar B.
通讯作者：
Malik, Asrar B.