| Autor: |
Xiangjie Chen, Qiuyu Wu, Xinhua Cao, Yunshan Yang, Zheng Gong, Tengfei Ren, Qian Du, Yukang Yuan, Yibo Zuo, Ying Miao, Jiuyi He, Caixia Qiao, Zhijin Zheng, Tingting Zhang, Yang Xu, Depei Wu, Qiao Wang, Lin Huang, Zhijun Xie, Haitao Lv, Jun Wang, Fangyuan Gong, Zhichun Liu, Chengping Wen, Hui Zheng |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
International immunopharmacology. 112 |
| ISSN: |
1878-1705 |
| Popis: |
Rheumatoid arthritis (RA) is an inflammatory autoimmune disease. RA development is mediated by the abnormal activation of multiple signaling pathways. Recent studies have revealed that type-I interferon (IFN-I) signaling plays an essential role in the occurrence and development of RA. However, how to target IFN-I signaling to develop anti-rheumatoid arthritis drugs remains largely unexplored. Here, our study showed that IFN-I signaling was over-activated in articular synovial cells from collagen II-induced arthritis (CIA) mice. Interestingly, we found that a small molecule compound, menthone, strongly inhibited the activation of the IFN-I signaling pathway. Further studies revealed that menthone promoted K48-linked polyubiquitination of Tyk2, thus lowering the protein level and stability of Tyk2. Importantly, menthone administration in the local articulus of CIA mice significantly attenuated the local inflammation in CIA mice. This study could promote our understanding of rheumatoid arthritis, and also suggests a potential strategy to develop anti-RA drugs. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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