| Literature DB >> 30566866 |
Senlin Li1, Ze Hong2, Zhe Wang3, Fei Li4, Jiahao Mei2, Lulu Huang5, Xiwen Lou6, Simeng Zhao4, Lihua Song2, Wei Chen5, Qiang Wang5, Heng Liu5, Yanni Cai5, Huansha Yu5, Huimin Xu4, Guangzhi Zeng4, Quanyi Wang2, Juanjuan Zhu2, Xing Liu7, Ninghua Tan8, Chen Wang9.
Abstract
cGAS-STING signaling is essential for innate immunity. Its misregulation promotes cancer or autoimmune and autoinflammatory diseases, and it is imperative to identify effective lead compounds that specifically downregulate the pathway. We report here that astin C, a cyclopeptide isolated from the medicinal plant Aster tataricus, inhibits cGAS-STING signaling and the innate inflammatory responses triggered by cytosolic DNAs. Moreover, mice treated with astin C are more susceptible to HSV-1 infection. Consistently, astin C markedly attenuates the autoinflammatory responses in Trex1-/- BMDM cells and in Trex1-/- mouse autoimmune disease model. Mechanistically, astin C specifically blocks the recruitment of IRF3 onto the STING signalosome. Collectively, this study characterizes a STING-specific small-molecular inhibitor that may be applied for potentially manipulating the STING-mediated clinical diseases.Entities:
Keywords: HSV-1; IRF3; STING; TBK1; astin C; autoimmune diseases; cGAS; cyclopeptide; innate immunity; therapeutic target
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Year: 2018 PMID： 30566866 DOI： 10.1016/j.celrep.2018.11.097
Source DB: PubMed Journal: Cell Rep Impact factor: 9.423