登录
 机构网站
  1. 首页
  2. 情报产品
  3. 快讯详情

《Nature，9月3日，COVID-19-activated SREBP2 disturbs cholesterol biosynthesis and leads to cytokine storm》

  • 来源专题：COVID-19科研动态监测
  • 编译者： zhangmin
  • 发布时间：2020-09-15

  • COVID-19-activated SREBP2 disturbs cholesterol biosynthesis and leads to cytokine storm
    Wonhwa Lee, June Hong Ahn, Hee Ho Park, Hong Nam Kim, Hyelim Kim, Youngbum Yoo, Hyosoo Shin, Kyung Soo Hong, Jong Geol Jang, Chun Gwon Park, Eun Young Choi, Jong-Sup Bae & Young-Kyo Seo
    Signal Transduction and Targeted Therapy volume 5, Article number: 186 (2020)

    Abstract
    Sterol regulatory element binding protein-2 (SREBP-2) is activated by cytokines or pathogen, such as virus or bacteria, but its association with diminished cholesterol levels in COVID-19 patients is unknown. Here, we evaluated SREBP-2 activation in peripheral blood mononuclear cells of COVID-19 patients and verified the function of SREBP-2 in COVID-19. Intriguingly, we report the first observation of SREBP-2 C-terminal fragment in COVID-19 patients’ blood and propose SREBP-2 C-terminal fragment as an indicator for determining severity. We confirmed that SREBP-2-induced cholesterol biosynthesis was suppressed by Sestrin-1 and PCSK9 expression, while the SREBP-2-induced inflammatory responses was upregulated in COVID-19 ICU patients. Using an infectious disease mouse model, inhibitors of SREBP-2 and NF-κB suppressed cytokine storms caused by viral infection and prevented pulmonary damages. These results collectively suggest that SREBP-2 can serve as an indicator for severity diagnosis and therapeutic target for preventing cytokine storm and lung damage in severe COVID-19 patients.

  • 原文来源：https://www.nature.com/articles/s41392-020-00292-7
10浏览量
原文链接
相关报告

  • 《9月3日_COVID-19激活的SREBP2干扰胆固醇的生物合成并导致细胞因子风暴》
    • 来源专题：COVID-19科研动态监测
    • 编译者：zhangmin
    • 发布时间：2020-09-15
    • 9月3日，韩国生物科学与生物技术研究所老化研究中心、庆南大学、江原国立大学、韩国科学技术研究院、忠南国立大学、成均馆大学和庆北国立大学的科研人员在Nature期刊在线发表题为“COVID-19-activated SREBP2 disturbs cholesterol biosynthesis and leads to cytokine storm”的文章。 研究表示，固醇调节元件结合蛋白-2（SREBP-2）可被细胞因子或病原体（如病毒或细菌）激活，但其与COVID-19患者胆固醇水平下降的关系尚不清楚。研究人员评估了SREBP-2在COVID-19患者外周血单核细胞中的激活情况，验证了SREBP-2在COVID-19中的作用。研究人员在COVID-19患者血液中观察到SREBP-2 C末端片段，并提出SREBP-2 C末端片段可作为判断病情严重程度的指标。研究人员证实，SREBP-2诱导的胆固醇生物合成被Sestrin-1和PCSK9表达抑制，而SREBP-2诱导的炎症反应在COVID-19 ICU患者中上调。使用传染性疾病小鼠模型发现SREBP-2和NF-κB抑制剂抑制病毒感染引起的细胞因子风暴，并预防肺损害。综上所述，SREBP-2不仅可作为COVID-19重度患者的严重性诊断指标，还可以作为预防细胞因子风暴和肺部损伤的治疗目标。 原文链接：https://www.nature.com/articles/s41392-020-00292-7
    59浏览量
    原文链接

  • 《Science，12月9日，Distinct inflammatory profiles distinguish COVID-19 from influenza with limited contributions from cytokine storm》
    • 来源专题：COVID-19科研动态监测
    • 编译者：zhangmin
    • 发布时间：2020-12-23
    • RESEARCH ARTICLECORONAVIRUS Distinct inflammatory profiles distinguish COVID-19 from influenza with limited contributions from cytokine storm View ORCID ProfilePhilip A. Mudd1,*,†, View ORCID ProfileJeremy Chase Crawford2,†, View ORCID ProfileJackson S. Turner3, View ORCID ProfileAisha Souquette2, Daniel Reynolds4, View ORCID ProfileD... Science Advances  09 Dec 2020: Vol. 6, no. 50, eabe3024 DOI: 10.1126/sciadv.abe3024 Abstract We pursued a study of immune responses in coronavirus disease 2019 (COVID-19) and influenza patients. Compared to patients with influenza, patients with COVID-19 exhibited largely equivalent lymphocyte counts, fewer monocytes, and lower surface human leukocyte antigen (HLA)–class II expression on selected monocyte populations. Furthermore, decreased HLA-DR on intermediate monocytes predicted severe COVID-19 disease. In contrast to prevailing assumptions, very few (7 of 168) patients with COVID-19 exhibited cytokine profiles indicative of cytokine storm syndrome. After controlling for multiple factors including age and sample time point, patients with COVID-19 exhibited lower cytokine levels than patients with influenza. Up-regulation of IL-6, G-CSF, IL-1RA, and MCP1 predicted death in patients with COVID-19 but were not statistically higher than patients with influenza. Single-cell transcriptional profiling revealed profound suppression of interferon signaling among patients with COVID-19. When considered across the spectrum of peripheral immune profiles, patients with COVID-19 are less inflamed than patients with influenza.
    17浏览量
    原文链接