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Citation: Jia Chen,  Cao Chen,  Chao Hu,  Lian Liu,  Ying Xia,  Lin Wang,  Wei Yang,  Hai-Yan Wu,  Wei Zhou,  Kang Xiao,  Qi Shi,  Yuezhang Wu,  Zhi-Bao Chen,  Xiao-Ping Dong. IP10, KC and M-CSF is Remarkably Increased in the Brains from the Various Strains of Experimental Mice Infected with Different Scrapie Agents [J].VIROLOGICA SINICA.  http://dx.doi.org/10.1007/s12250-020-00216-3

IP10, KC and M-CSF is Remarkably Increased in the Brains from the Various Strains of Experimental Mice Infected with Different Scrapie Agents

  • Activation of inflammatory cells and upregulations of a number of cytokines in the central nervous system (CNS) of patients with prion diseases are frequently observed. To evaluate the potential changes of some brain cytokines that were rarely addressed during prion infection, the levels of 17 different cytokines in the brain homogenates of mice infected with different scrapie mouse-adapted agents were firstly screened with Luminex assay. Significant upregulations of interferon gamma-induced protein 10 (IP10), keratinocyte chemoattractant (KC) and macrophage colony stimulating factor (M-CSF) were frequently detected in the brain lysates of many strains of scrapie infected mice. The upregulations of those three cytokines in the brains of scrapie infected mice were further validated by the individual specific ELISA and immunohistochemical assay. Increased specific mRNAs of IP10, M-CSF and KC in the brains of scrapie infected mice were also detected by the individual specific qRT-PCRs and IP10-specific digital PCR. Dynamic analyses of the brain samples collected at different time points post infection revealed the time-dependent increases of those three cytokines, particularly IP10 during the incubation period of scrapie infection. In addition, we also found that the levels of IP10 in cerebral spinal fluid (CSF) of 45 sporadic Creutzfeldt–Jakob disease (sCJD) patients were slightly but significantly higher than those of the cases who were excluded the diagnosis of prion diseases. These data give us a better understanding of inflammatory reaction during prion infection and progression of prion disease.

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    IP10, KC and M-CSF is Remarkably Increased in the Brains from the Various Strains of Experimental Mice Infected with Different Scrapie Agents

      Corresponding author: Cao Chen, chencao@ivdc.chinacdc.cn
      Corresponding author: Zhi-Bao Chen, chenzb@gdou.edu.cn
      Corresponding author: Xiao-Ping Dong, dongxp238@sina.com
    • 1 College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163000, China
    • 2 State Key Laboratory of Infectious Disease Prevention and Control, NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100000, China
    • 3 Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou 310000, China
    • 4 Center for Global Public Health, Chinese Center for Disease Control and Prevention, Beijing 100000, China
    • 5 Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan 430000, China
    • 6 China Academy of Chinese Medical Sciences, Beijing 100000, China
    • 7 College of Life Science and Technology, Heilongjiang Bayi Agricultural University, Daqing 163000, China

    Abstract: Activation of inflammatory cells and upregulations of a number of cytokines in the central nervous system (CNS) of patients with prion diseases are frequently observed. To evaluate the potential changes of some brain cytokines that were rarely addressed during prion infection, the levels of 17 different cytokines in the brain homogenates of mice infected with different scrapie mouse-adapted agents were firstly screened with Luminex assay. Significant upregulations of interferon gamma-induced protein 10 (IP10), keratinocyte chemoattractant (KC) and macrophage colony stimulating factor (M-CSF) were frequently detected in the brain lysates of many strains of scrapie infected mice. The upregulations of those three cytokines in the brains of scrapie infected mice were further validated by the individual specific ELISA and immunohistochemical assay. Increased specific mRNAs of IP10, M-CSF and KC in the brains of scrapie infected mice were also detected by the individual specific qRT-PCRs and IP10-specific digital PCR. Dynamic analyses of the brain samples collected at different time points post infection revealed the time-dependent increases of those three cytokines, particularly IP10 during the incubation period of scrapie infection. In addition, we also found that the levels of IP10 in cerebral spinal fluid (CSF) of 45 sporadic Creutzfeldt–Jakob disease (sCJD) patients were slightly but significantly higher than those of the cases who were excluded the diagnosis of prion diseases. These data give us a better understanding of inflammatory reaction during prion infection and progression of prion disease.

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