Ester alkaloids from Cephalotaxus interfere with the 2'3'-cGAMP-induced type I interferon pathway in vitro
- Authors
- Park, Gayoung; Kim, Sun Yeou; Song, Yoon-Jae
- Issue Date
- 3-Aug-2017
- Publisher
- PUBLIC LIBRARY SCIENCE
- Citation
- PLOS ONE, v.12, no.8
- Journal Title
- PLOS ONE
- Volume
- 12
- Number
- 8
- URI
- https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/5824
- DOI
- 10.1371/journal.pone.0182701
- ISSN
- 1932-6203
- Abstract
- Dysregulated activation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway by self-DNA contributes to interferonopathy and promotes autoimmune diseases. To identify potential suppressors of STING-induced type I interferon (IFN) induction, ethanol extracts of medicinal plants were screened for inhibitory activity against IFN-beta promoter activation. Notably, 70% ethanol extract of Cephalotaxus koreana specifically down-regulated STING-induced, but not TBK1-or IRF3-induced, IFN-beta promoter activity. The compounds exerting inhibitory activity specifically against STING-mediated IFN-beta promoter activation were identified as ester alkaloids isolated from the genus, Cephalotaxus, homoharringtonine and harringtonine. Furthermore, these two compounds inhibited 2'3'-cGAMP-induced IFN-stimulated gene expression and interaction between STING and TBK1. These suppressive effects were not observed with cephalotaxine devoid of the ester side-chain. Our data support the potential utility of homoharringtonine and harringtonine to treat STING-associated interferonopathy and autoimmune diseases.
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Collections - 바이오나노대학 > 생명과학과 > 1. Journal Articles
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