Succinate Is an Inflammation-Induced Immunoregulatory Metabolite in Macrophages.
Succinate Is an Inflammation-Induced Immunoregulatory Metabolite in Macrophages.
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DOI：
10.3390/metabo10090372
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发表时间：
2020-09-15
期刊：
影响因子：
4.1
通讯作者：
Van den Bossche J
中科院分区：
文献类型：
--
作者：
Harber KJ;de Goede KE;Verberk SGS;Meinster E;de Vries HE;van Weeghel M;de Winther MPJ;Van den Bossche J
免疫代谢揭示了细胞代谢在控制免疫细胞表型和功能中的关键作用。巨噬细胞是支持许多炎性疾病进展的关键免疫细胞，已被充分描述为在激活后经历大量代谢重新布线。特别是免疫代谢物琥珀酸酯获得了很多关注，并成为巨噬细胞反应和炎症的关键调节剂。琥珀酸盐最初被描述为通过不同途径支持炎症的代谢物。最近，研究表明琥珀酸及其受体SUCNR 1也可以抑制免疫反应。这些明显矛盾的影响可能是由于特定的实验设置，特别是不同的琥珀酸盐形式的使用。因此，我们比较了以前用于研究琥珀酸免疫调节的不同琥珀酸盐形式和受体小鼠模型的表型和功能效应。在这里，我们表明，琥珀酸可以抑制炎症介质IL-6，肿瘤坏死因子（TNF）和一氧化氮（NO）的分泌，以及抑制炎症巨噬细胞的IL 1b mRNA表达的SUCNR 1-独立的方式。我们还观察到，巨噬细胞SUCNR 1缺陷导致增强的炎症反应，而不添加外源性琥珀酸。虽然我们的研究没有揭示琥珀酸如何激发不同炎症反应的新机制，但它确实表明琥珀酸及其受体SUCNR 1在巨噬细胞中的炎症作用明显依赖于环境。
Immunometabolism revealed the crucial role of cellular metabolism in controlling immune cell phenotype and functions. Macrophages, key immune cells that support progression of numerous inflammatory diseases, have been well described as undergoing vast metabolic rewiring upon activation. The immunometabolite succinate particularly gained a lot of attention and emerged as a crucial regulator of macrophage responses and inflammation. Succinate was originally described as a metabolite that supports inflammation via distinct routes. Recently, studies have indicated that succinate and its receptor SUCNR1 can suppress immune responses as well. These apparent contradictory effects might be due to specific experimental settings and particularly the use of distinct succinate forms. We therefore compared the phenotypic and functional effects of distinct succinate forms and receptor mouse models that were previously used for studying succinate immunomodulation. Here, we show that succinate can suppress secretion of inflammatory mediators IL-6, tumor necrosis factor (TNF) and nitric oxide (NO), as well as inhibit Il1b mRNA expression of inflammatory macrophages in a SUCNR1-independent manner. We also observed that macrophage SUCNR1 deficiency led to an enhanced inflammatory response without addition of exogenous succinate. While our study does not reveal new mechanistic insights into how succinate elicits different inflammatory responses, it does indicate that the inflammatory effects of succinate and its receptor SUCNR1 in macrophages are clearly context dependent.
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Itaconate连接琥珀酸脱氢酶与巨噬细胞代谢重塑和调节炎症的联系。
影响因子：
29
作者：
Lampropoulou V;Sergushichev A;Bambouskova M;Nair S;Vincent EE;Loginicheva E;Cervantes-Barragan L;Ma X;Huang SC;Griss T;Weinheimer CJ;Khader S;Randolph GJ;Pearce EJ;Jones RG;Diwan A;Diamond MS;Artyomov MN
通讯作者：
Artyomov MN
影响因子：
64.8
作者：
He, WH;Miao, FJP;Ling, L
通讯作者：
Ling, L
DOI：
10.1084/jem.20151570
发表时间：
2016-01-11
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
O'Neill LA;Pearce EJ
通讯作者：
Pearce EJ
影响因子：
30.5
作者：
Rubic, Tina;Lametschwandtner, Guenther;Carballido, Jose M.
通讯作者：
Carballido, Jose M.
DOI：
10.1042/bj20111386
发表时间：
2011-09-15
期刊：
The Biochemical journal
影响因子：
--
作者：
O'Neill, Luke A J
通讯作者：
O'Neill, Luke A J