2. Academic Validation
  3. Menthone inhibits type-I interferon signaling by promoting Tyk2 ubiquitination to relieve local inflammation of rheumatoid arthritis

Menthone inhibits type-I interferon signaling by promoting Tyk2 ubiquitination to relieve local inflammation of rheumatoid arthritis

  • Int Immunopharmacol. 2022 Nov:112:109228. doi: 10.1016/j.intimp.2022.109228.
Xiangjie Chen 1,  Qiuyu Wu 1,  Xinhua Cao 1,  Yunshan Yang 2,  Zheng Gong 1,  Tengfei Ren 1,  Qian Du 1,  Yukang Yuan 1,  Yibo Zuo 1,  Ying Miao 1,  Jiuyi He 1,  Caixia Qiao 1,  Zhijin Zheng 1,  Tingting Zhang 1,  Yang Xu 3,  Depei Wu 3,  Qiao Wang 4,  Lin Huang 4,  Zhijun Xie 4,  Haitao Lv 5,  Jun Wang 6,  Fangyuan Gong 1,  Zhichun Liu 7,  Chengping Wen 4,  Hui Zheng 8
Affiliations

Affiliations

  • 1 Institutes of Biology and Medical Sciences, Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou 215123, Jiangsu, China.
  • 2 Medical College of Soochow University, Suzhou 215123, Jiangsu, China.
  • 3 Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou 215123, Jiangsu, China.
  • 4 College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China.
  • 5 Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou 215123, Jiangsu, China.
  • 6 Department of Intensive Care Medicine, the First Affiliated Hospital of Soochow University, Suzhou 215123, Jiangsu, China.
  • 7 Department of Rheumatology and Immunology, The Second Affiliated Hospital of Soochow University, Suzhou 215123, Jiangsu, China.
  • 8 Institutes of Biology and Medical Sciences, Jiangsu Key Laboratory of Infection and Immunity, Soochow University, Suzhou 215123, Jiangsu, China. Electronic address: [email protected].
PMID: 36095947 DOI: 10.1016/j.intimp.2022.109228
Abstract

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.

Keywords

Interferon; Menthone; Rheumatoid arthritis; Tyk2; Ubiquitination.

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