当前位置: X-MOL 学术Proc. Natl. Acad. Sci. U.S.A. › 论文详情
HIF-1{alpha} is a negative regulator of interferon regulatory factors: Implications for interferon production by hypoxic monocytes [Immunology and Inflammation]
Proceedings of the National Academy of Sciences of the United States of America ( IF 9.412 ) Pub Date : 2021-06-29 , DOI: 10.1073/pnas.2106017118
Travis Peng, Shin-Yi Du, Myoungsun Son, Betty Diamond

Patients with severe COVID-19 infection exhibit a low level of oxygen in affected tissue and blood. To understand the pathophysiology of COVID-19 infection, it is therefore necessary to understand cell function during hypoxia. We investigated aspects of human monocyte activation under hypoxic conditions. HMGB1 is an alarmin released by stressed cells. Under normoxic conditions, HMGB1 activates interferon regulatory factor (IRF)5 and nuclear factor-κB in monocytes, leading to expression of type I interferon (IFN) and inflammatory cytokines including tumor necrosis factor α, and interleukin 1β, respectively. When hypoxic monocytes are activated by HMGB1, they produce proinflammatory cytokines but fail to produce type I IFN. Hypoxia-inducible factor-1α, induced by hypoxia, functions as a direct transcriptional repressor of IRF5 and IRF3. As hypoxia is a stressor that induces secretion of HMGB1 by epithelial cells, hypoxia establishes a microenvironment that favors monocyte production of inflammatory cytokines but not IFN. These findings have implications for the pathogenesis of COVID-19.



中文翻译:

HIF-1{alpha} 是干扰素调节因子的负调节因子:对缺氧单核细胞产生干扰素的影响 [免疫学和炎症]

患有严重 COVID-19 感染的患者在受影响的组织和血液中表现出低氧水平。因此,要了解 COVID-19 感染的病理生理学,就必须了解缺氧期间的细胞功能。我们研究了缺氧条件下人类单核细胞活化的各个方面。HMGB1 是应激细胞释放的警报。在常氧条件下,HMGB1 激活单核细胞中的干扰素调节因子 (IRF)5 和核因子-κB,分别导致 I 型干扰素 (IFN) 和炎性细胞因子(包括肿瘤坏死因子 α 和白细胞介素 1β)的表达。当缺氧单核细胞被 HMGB1 激活时,它们产生促炎细胞因子但不能产生 I 型干扰素。缺氧诱导的缺氧诱导因子-1α,作为 IRF5 和 IRF3 的直接转录抑制因子起作用。由于缺氧是诱导上皮细胞分泌 HMGB1 的压力源,缺氧会建立一个有利于单核细胞产生炎性细胞因子而不是 IFN 的微环境。这些发现对 COVID-19 的发病机制具有重要意义。

更新日期:2021-06-10
全部期刊列表>>
virulence
欢迎新作者ACS
中国作者高影响力研究精选
虚拟特刊
屿渡论文,编辑服务
浙大
上海中医药大学
深圳大学
上海交通大学
南方科技大学
浙江大学
清华大学
徐晶
张大卫
彭孝军
北京大学
隐藏1h前已浏览文章
课题组网站
新版X-MOL期刊搜索和高级搜索功能介绍
ACS材料视界
华辉
天合科研
x-mol收录
试剂库存
down
wechat
bug