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

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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Acknowledgements

This work was supported by the National Natural Science Foundation of China (81772197, 81401670 and 81630062), the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (2018RC330004), National Key R&D Program of China (2018YFC1200305Y), National Science and Technology Major Project of China (2018ZX10102001), SKLID Development Grant (2019SKLID401 and 2016SKLID603) and the Natural Science Foundation of Heilongjiang Province (C2018044).

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JC and CC performed most of the experiments and drafted the manuscript. JC and WZ carried out the Western blot and Luminex assay. JC and CH performed ELISA. JC, YZW and LL carried out the IHC, JC and YX carried out the real-time PCR and digital PCR. CC, QS, KX and ZBC performed the statistical analysis. CC, ZBC and XPD conceived of the study and finalized the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Cao Chen or Zhi-Bao Chen or Xiao-Ping Dong.

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All the authors declare that they have no conflict of interest.

Animal and Human Rights Statement

All procedures were approved and supervised by the Ethical Committee of the National Institute for Viral Disease Control and Prevention, China CDC. Usage of stored human CSF samples in the Center of Chinese CJD Surveillance System has been approved by the Ethics Committee of the National Institute for Viral Disease Control and Prevention, China CDC.

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Chen, J., Chen, C., Hu, C. et al. IP10, KC and M-CSF Are Remarkably Increased in the Brains from the Various Strains of Experimental Mice Infected with Different Scrapie Agents. Virol. Sin. (2020). https://doi.org/10.1007/s12250-020-00216-3

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Keywords

  • Prion
  • Cytokines
  • Interferon gamma-induced protein 10 (IP10)
  • Keratinocyte chemoattractant (KC)
  • Macrophage colony stimulating factor (M-CSF)