ReferenceID 2037

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

Int Immunopharmacol

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

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Reference Id
2037
Evidence Id
18627
Core Evidence Id
18627
Source Reference Id
4449
Herb2 Reference Id
HBREF005246
Subject Paper Key
HBIN033440_36095947
Pubmed Id
36095947
Doi
10.1016/j.intimp.2022.109228
Paper Title
Menthone inhibits type-I interferon signaling by promoting Tyk2 ubiquitination to relieve local inflammation of rheumatoid arthritis
Paper 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.
Journal
Int Immunopharmacol
Publish Year
2022
Experiment Subject
mouse
Experiment Type
Animal Experiment
Phenotype Related
Arthritis; Rheumatoid Arthritis; Anti-ra; Anti-rheumatoid Arthritis; Inflammatory Autoimmune Disease
Paper Title Cn
Paper Title En
Menthone inhibits type-I interferon signaling by promoting Tyk2 ubiquitination to relieve local inflammation of rheumatoid arthritis
Bilingual Status
semi_complete