Activation of IP10/CXCR3 Signaling is Highly Coincidental with PrP Deposition in the Brains of Scrapie-Infected Mice.
作者信息
Jia Chen, Cao Chen, Chao Hu, Wei Yang, Lin Wang, Dongdong Chen, Yuezhang Wu, Qi Shi, Xiaoping Dong
机构信息
National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, NHC Key Laboratory for Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, NHC Key Laboratory for Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China;Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou 100084, Zhejiang, China;Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430071, Hubei, China.
出版信息
Biomed Environ Sci. 2024 Nov 20;37(11):1235-1251. doi: 10.3967/bes2024.158.
OBJECTIVE
To analyze the relationship between Chemokine IP10 and its receptor CXCR3 during prion infection.
METHODS
We investigated the increases in IP10 signals, primarily localized in neurons within the brains of scrapie-infected mice, using western blotting, ELISA, co-immunoprecipitation, immunohistochemistry, immunofluorescence assays, and RT-PCR.
RESULTS
Both CXCR3 levels and activation were significantly higher in the brains of scrapie-infected mice and prion-infected SMB-S15 cells. Enhanced CXCR3 expression was predominantly observed in neurons and activated microglia. Morphological colocalization of PrP /PrP with IP10/CXCR3 was observed in scrapie-infected mouse brains using immunohistochemistry and immunofluorescence. immunohistochemistry (IHC) analysis of whole brain sections further revealed increased accumulation of IP10/CXCR3 specifically in brain regions with higher levels of PrP deposits. Co-immunoprecipitation and biomolecular interaction assays revealed the molecular interactions between PrP and IP10/CXCR3. Notably, a significantly larger amount of IP10 accumulated within prion-infected SMB-S15 cells than in the normal partner cell line, SMB-PS. Importantly, resveratrol treatment effectively suppressed prion replication in SMB-S15 cells, thereby restoring the accumulation and secretion pattern of cellular IP10 similar to that observed in SMB-PS cells.
CONCLUSION
Our data demonstrate that the activation of IP10/CXCR3 signaling in prion-infected brain tissues coincides with PrP deposition. Modulation of IP10/CXCR3 signaling in the brain represents a potential therapeutic target for mitigating the progression of prion diseases.
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