Activation of IP10/CXCR3 Signaling is Highly Coincidental with PrP^(Sc)Deposition in the Brains of Scrapie-Infected Mice  

作　　者：Chen Jia Chen Cao Hu Chao Yang Wei Wang Lin Chen Dongdong Wu Yuezhang Shi Qi Dong Xiaoping 

机构地区：[1]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 [2]Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases,Zhejiang University,Hangzhou 100084,Zhejiang,China [3]Center for Biosafety Mega-Science,Chinese Academy of Sciences,Wuhan 430071,Hubei,China [4]China Academy of Chinese Medical Sciences,Beijing 100700,China [5]Shanghai Institute of Infectious Disease and Biosafety,Shanghai 200003,China

出　　处：《Biomedical and Environmental Sciences》2024年第11期1235-1251,共17页生物医学与环境科学（英文版）

基　　金：supported by SKLID Development Grants(2021SKLID504,2019SKLID401,2019SKLID603,and 2016SKLID603);the National Natural Science Foundation of China(81772197,81401670,and 81630062)。

摘　　要：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 PrPC/PrPSc 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 PrPSc 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 PrPSc deposition.Modulation of IP10/CXCR3 signaling in the brain represents a potential therapeutic target for mitigating the progression of prion diseases.

关 键 词：PRION Chemokine IP10 CXCR3 ACTIVATION 

分 类 号：R741[医药卫生—神经病学与精神病学]