High-salt diet downregulates TREM2 expression and blunts efferocytosis of macrophages after acute ischemic stroke.
High-salt diet downregulates TREM2 expression and blunts efferocytosis of macrophages after acute ischemic stroke.
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高盐饮食下调 TREM2 表达并减弱急性缺血性中风后巨噬细胞的胞吞作用。
DOI：
10.1186/s12974-021-02144-9
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发表时间：
2021-04-12
影响因子：
9.3
通讯作者：
Lu Z
中科院分区：
文献类型：
--
作者：
Hu M;Lin Y;Men X;Wang S;Sun X;Zhu Q;Lu D;Liu S;Zhang B;Cai W;Lu Z
高盐饮食是急性缺血性脑卒中（AIS）的主要危险因素之一。作为一种潜在的机制，过量的盐摄入使巨噬细胞向促炎表型转变。本研究探讨HSD是否会钝化缺血性脑卒中后巨噬细胞的红细胞生成能力，从而加重脑卒中后神经炎症。野生型雄性C57BL/6小鼠饲喂含8%氯化钠的饲料4周后，进行短暂性大脑中闭塞（tMCAO）。评估疾病严重程度、巨噬细胞极化和红细胞功能。体外培养骨髓源性巨噬细胞，分析高盐度对骨髓源性巨噬细胞的吞噬活性及吞噬分子表达的影响。探讨AIS患者钠浓度、巨噬细胞表型与疾病严重程度之间的关系。hsd喂养的小鼠显示梗死面积增加，神经功能缺陷加重。HSD喂养的小鼠神经炎症加重，炎症介质表达和免疫细胞浸润水平升高。在hsd喂养的小鼠脑卒中病变内浸润的巨噬细胞表现出向促炎表型的转变和受损的红细胞功能。PCR检测结果显示，在高盐处理的骨髓源性巨噬细胞中，与吞噬作用相关的骨髓源性巨噬细胞触发受体2 （TREM2）的表达下调。TREM2信号的增强恢复了巨噬细胞在体外和体内高盐度环境下的红细胞生成能力和细胞炎症消退能力。研究发现，AIS患者尿钠浓度高与TREM2表达降低和卒中预后不良相关。HSD通过下调TREM2的表达抑制巨噬细胞的红细胞生成能力，从而阻碍缺血性脑卒中后炎症的消退。增强单核/巨噬细胞中的TREM2信号可能是一种有希望的治疗策略，可以增强脑卒中后的efferocytosis和促进炎症消退。在线版本包含补充材料，可在10.1186/s12974-021-02144-9获得。
A high-salt diet (HSD) is one of the major risk factors for acute ischemic stroke (AIS). As a potential mechanism, surplus salt intake primes macrophages towards a proinflammatory phenotype. In this study, whether HSD could blunt the efferocytic capability of macrophages after ischemic stroke, thus exacerbating post-stroke neural inflammation, was investigated. Wild-type male C57BL/6 mice were fed with fodder containing 8% sodium chloride for 4 weeks and subjected to transient middle cerebral occlusion (tMCAO). Disease severity, macrophage polarization as well as efferocytic capability were evaluated. Bone marrow-derived macrophages were cultured in vitro, and the impact of high salinity on their efferocytic activity, as well as their expression of phagocytic molecules, were analyzed. The relationships among sodium concentration, macrophage phenotype, and disease severity in AIS patients were explored. HSD-fed mice displayed increased infarct volume and aggravated neurological deficiency. Mice fed with HSD suffered exacerbated neural inflammation as shown by higher inflammatory mediator expression and immune cell infiltration levels. Infiltrated macrophages within stroke lesions in HSD-fed mice exhibited a shift towards proinflammatory phenotype and impaired efferocytic capability. As assessed with a PCR array, the expression of triggering receptor expressed on myeloid cells 2 (TREM2), a receptor relevant to phagocytosis, was downregulated in high-salt-treated bone marrow-derived macrophages. Enhancement of TREM2 signaling restored the efferocytic capacity and cellular inflammation resolution of macrophages in a high salinity environment in vitro and in vivo. A high concentration of urine sodium in AIS patients was found to be correlated with lower TREM2 expression and detrimental stroke outcomes. HSD inhibited the efferocytic capacity of macrophages by downregulating TREM2 expression, thus impeding inflammation resolution after ischemic stroke. Enhancing TREM2 signaling in monocytes/macrophages could be a promising therapeutic strategy to enhance efferocytosis and promote post-stroke inflammation resolution. The online version contains supplementary material available at 10.1186/s12974-021-02144-9.
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影响因子：
14.5
作者：
Jackson, C;Sudlow, C
通讯作者：
Sudlow, C
影响因子：
25
作者：
Faraco G;Brea D;Garcia-Bonilla L;Wang G;Racchumi G;Chang H;Buendia I;Santisteban MM;Segarra SG;Koizumi K;Sugiyama Y;Murphy M;Voss H;Anrather J;Iadecola C
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Iadecola C
DOI：
10.1016/j.tem.2018.08.004
发表时间：
2018-10
期刊：
Trends in endocrinology and metabolism: TEM
影响因子：
--
作者：
Wein MN;Foretz M;Fisher DE;Xavier RJ;Kronenberg HM
通讯作者：
Kronenberg HM
影响因子：
20.1
作者：
O'Donnell, Martin;Mente, Andrew;Yusuf, Salim
通讯作者：
Yusuf, Salim
影响因子：
8
作者：
Cai, Wei;Dai, Xuejiao;Chen, Jun
通讯作者：
Chen, Jun