Identification of serum metabolites enhancing inflammatory responses in COVID-19.
Identification of serum metabolites enhancing inflammatory responses in COVID-19.
复制标题
鉴定增强 COVID-19 炎症反应的血清代谢物。
DOI：
10.1007/s11427-021-2099-7
复制
发表时间：
2022-10
影响因子：
9.1
通讯作者：
Wang, Zhanxiang
中科院分区：
文献类型：
--
作者：
Zhang, Chen-Song;Zhang, Bingchang;Li, Mengqi;Wei, Xiaoyan;Gong, Kai;Li, Zhiyong;Yao, Xiangyang;Wu, Jianfeng;Zhang, Cixiong;Zhu, Mingxia;Zhang, Lei;Sun, Xiufeng;Zhan, Yi-Hong;Jiang, Zhengye;Zhao, Wenpeng;Zhong, Wei;Zhuang, Xinguo;Zhou, Dawang;Piao, Hai-Long;Lin, Sheng-Cai;Wang, Zhanxiang
2019年冠状病毒病(新冠肺炎)由严重急性呼吸综合征冠状病毒2(SARS-CoV-2)引起，其特点是强烈产生肿瘤坏死因子和IL-6等炎性细胞因子，这是疾病严重程度的基础。然而，导致如此强烈的免疫反应的分子机制仍不清楚。在这里，利用靶向串联质谱仪分析不同时间段新冠肺炎患者的血清代谢组和脂质体，我们发现1,039种代谢物中的611种在新冠肺炎患者中显著改变。其中，胍丁胺和腐胺两种代谢物在患者血清中显著升高；2-喹啉甲酸呈双相变化，在新冠肺炎感染早期升高，后趋于平稳。当在小鼠胚胎成纤维细胞(MEF)和巨噬细胞中测试时，这3种代谢物被发现激活了在调节细胞因子产生中起关键作用的NF-κB途径。重要的是，当给予野生型小鼠时，这些代谢物都能引起肿瘤坏死因子和白介素6水平的显著增加，但在缺乏核因子-κB的小鼠中则不然。有趣的是，这些代谢物对干扰素调节因子(IRF)的激活几乎没有影响，这些干扰素调节因子(IFF)用于产生用于抗病毒防御的I型干扰素(IFN)。这些数据表明，新冠肺炎感染引起的循环代谢产物可能作为效应器，诱导特殊的全身炎症反应，表现出极强的促炎细胞因子产生，而干扰素的诱导有限。我们的研究可能为开发减轻新冠肺炎患者炎症的药物提供理论依据。支持信息可在线查阅，电话：10.1007/s114270212099-7。支持材料按提交的方式出版，不进行排版或编辑。科学准确性和内容的责任完全在作者身上。
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is characterized by a strong production of inflammatory cytokines such as TNF and IL-6, which underlie the severity of the disease. However, the molecular mechanisms responsible for such a strong immune response remains unclear. Here, utilizing targeted tandem mass spectrometry to analyze serum metabolome and lipidome in COVID-19 patients at different temporal stages, we identified that 611 metabolites (of 1,039) were significantly altered in COVID-19 patients. Among them, two metabolites, agmatine and putrescine, were prominently elevated in the serum of patients; and 2-quinolinecarboxylate was changed in a biphasic manner, elevated during early COVID-19 infection but levelled off. When tested in mouse embryonic fibroblasts (MEFs) and macrophages, these 3 metabolites were found to activate the NF-κB pathway that plays a pivotal role in governing cytokine production. Importantly, these metabolites were each able to cause strong increase of TNF and IL-6 levels when administered to wildtype mice, but not in the mice lacking NF-κB. Intriguingly, these metabolites have little effects on the activation of interferon regulatory factors (IRFs) for the production of type I interferons (IFNs) for antiviral defenses. These data suggest that circulating metabolites resulting from COVID-19 infection may act as effectors to elicit the peculiar systemic inflammatory responses, exhibiting severely strong proinflammatory cytokine production with limited induction of the interferons. Our study may provide a rationale for development of drugs to alleviate inflammation in COVID-19 patients. The supporting information is available online at 10.1007/s11427-021-2099-7. The supporting materials are published as submitted, without typesetting or editing. The responsibility for scientific accuracy and content remains entirely with the authors.
登录
查看更多内容
影响因子：
4
作者：
Berry CT;May MJ;Freedman BD
通讯作者：
Freedman BD
影响因子：
16.6
作者：
Gassen NC;Papies J;Bajaj T;Emanuel J;Dethloff F;Chua RL;Trimpert J;Heinemann N;Niemeyer C;Weege F;Hönzke K;Aschman T;Heinz DE;Weckmann K;Ebert T;Zellner A;Lennarz M;Wyler E;Schroeder S;Richter A;Niemeyer D;Hoffmann K;Meyer TF;Heppner FL;Corman VM;Landthaler M;Hocke AC;Morkel M;Osterrieder N;Conrad C;Eils R;Radbruch H;Giavalisco P;Drosten C;Müller MA
通讯作者：
Müller MA
影响因子：
168.9
作者：
Huang, Chaolin;Wang, Yeming;Cao, Bin
通讯作者：
Cao, Bin
影响因子：
16.2
作者：
Lu, Jieli;Lam, Sin Man;Wang, Weiqing
通讯作者：
Wang, Weiqing
影响因子：
82.9
作者：
Del Valle DM;Kim-Schulze S;Huang HH;Beckmann ND;Nirenberg S;Wang B;Lavin Y;Swartz TH;Madduri D;Stock A;Marron TU;Xie H;Patel M;Tuballes K;Van Oekelen O;Rahman A;Kovatch P;Aberg JA;Schadt E;Jagannath S;Mazumdar M;Charney AW;Firpo-Betancourt A;Mendu DR;Jhang J;Reich D;Sigel K;Cordon-Cardo C;Feldmann M;Parekh S;Merad M;Gnjatic S
通讯作者：
Gnjatic S