探索先天免疫,海巡署蛋白质,和我们自己的DNA受损
![Inhibition of human and mouse cGAS with RU.521 reduces interferon expression in multiple cell types. Lines used were: THP-1 and its derivatives (a–c), RAW 267.4 (d), and HEK293 (e–g) cells. THP-1 KO-cGAS cells were transfected with either vector plasmid control or a plasmid containing h-cGAS, and treated with either vehicle (DMSO) or RU.521 (a, left panel). WT THP-1 cells were mock treated (unt) or stimulated with 0.3 µg/mL HT-DNA +/− RU.521, followed by RT-qPCR analysis for IFNB1 expression (a, right panel). An ELISA for human IFNB1 was also performed on THP-1 cells stimulated with HT-DNA +/− RU.521 (0.8 µM) (b). A dose-response curve was generated for RU.521 using immune-activated THP-1 Lucia ISG cells (c). RAW-Lucia ISG KO cGAS cells were transfected with plasmids expressing WT m-cGAS or h-cGAS, and activity was read via luciferase reporter (d). HEK293 cells were transfected with human or mouse cGAS in addition to h-STING, in the presence or absence of RU.521. The RNA levels for IFNB1 and IFIT2 were then measured by RT-qPCR (e,f). Transfection of vector backbone was used to normalize the data. Immunoblot analysis of transfected h-STING, h-cGAS and m-cGAS into HEK293 cells +/− RU.521 shows protein expression is unaltered by addition of the small molecule. GM130 was used to normalize the data (g). The minimum numbers of biological and technical replicates for the assays were three and three, respectively (n = 9). Error bars represent SEM. Asterisks (*) denote P ≤ 0.05 where an unpaired t-test with Welch’s correction was used to compare the results. Credit: <i>Scientific Reports</i> (2020). DOI: 10.1038/s41598-020-64348-y 探索先天免疫](https://scx1.b-cdn.net/csz/news/800a/2020/probinginnat.jpg)
注册会计师的蛋白质在细胞的先天免疫中扮演着重要的角色的DNA检测入侵的病原体如细菌和病毒,或我们自己的损坏和mislocalized DNA。cGAS-STING信号通路的激活产生促炎症免疫反应,和长时间激活注册会计师可能导致lupus-like自身免疫性疾病。
Manuel Ascano博士和他的同事发现的复合RU.521作为抑制剂鼠标注册会计师。他们现在也证明RU.521强有力地和有选择性地抑制人类的注册会计师细胞系和人类的主要细胞。他们表明RU.521剂量依赖性抑制海巡署活动方式,不抑制免疫反应激活非dna的信号。
这项研究发表在5月5日科学报告,验证使用RU.521作为一种工具来评估的贡献cGAS-STING信号轴在不同的免疫反应。复合也可以作为化学脚手架cGAS-related的潜在治疗自身免疫性疾病的发展。
更多信息:卡罗琳明智et al。小分子抑制人类的海巡署减少cGAMP总产量和细胞内细胞因子的表达,科学报告(2020)。DOI: 10.1038 / s41598 - 020 - 64348 - y
期刊信息:
科学报告
所提供的范德比尔特大学
引用:探索先天免疫,海巡署蛋白质,和我们自己的DNA受损(2020年5月22日)检索2022年11月14日从//www.puressens.com/news/2020-05-probing-innate-immunity-cgas-protein.html
本文档版权。除了任何公平交易私人学习或研究的目的,没有书面许可,不得部分复制。内容只提供信息的目的。