Abstract
Despite the overwhelming evidence of the involvement of prion protein (PrP) in prion disease pathogenesis, the normal functions of this cell surface glycoprotein remain unclear. Previously, we showed that PrP may have a dual regulatory role by regulating the opposite poles of pro-inflammation and anti-inflammation as well as tissue repair in activated microglia. In the present work, we compared the mRNA expression of inflammation-related cytokines (TNF-α, IL-1β, IL-6, NOS2, and IL-10) and IL-4-related alternative activation markers (Arg1 and Mrc1) after lipopolysaccharide (LPS) challenge in the brain and spleen and examined peripheral leukocyte recovery and LPS-induced mortality in PrP knockout mice (PrP−/−) and wild-type (WT) mice. During the acute phase, WT mice exhibited higher levels of pro-inflammatory cytokines in the brain and spleen than in PrP−/− mice, while PrP−/− mice sustained higher levels of pro-inflammatory cytokines and lower levels of anti-inflammatory cytokines, Arg1, and Mrc1 during the later phase. PrP−/− mice also exhibited a slower peripheral leukocyte recovery process and higher mortality in response to LPS-induced septic shock. These results suggest that the PrP may participate in the protection of mice from LPS infection by regulating the process of inflammatory response.
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Acknowledgments
This work was supported by the National “12th Five-Year” Plan for Science & Technology Support (Project No.2012AA101302), MoSTRCUK International Cooperation project (Project No. 2013DFG32500), National Natural Science Foundation (Project No.31172293, No.31272532), Chinese Universities Scientific Fund (Project No.2013QT004), and 2013 CAU Foreign Experts Major Projects (project NO.2012Z018).
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The authors declare no financial or commercial conflicts of interest.
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Jin Liu and Deming Zhao contributed equally to this work.
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Liu, J., Zhao, D., Liu, C. et al. Prion Protein Participates in the Protection of Mice from Lipopolysaccharide Infection by Regulating the Inflammatory Process. J Mol Neurosci 55, 279–287 (2015). https://doi.org/10.1007/s12031-014-0319-2
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DOI: https://doi.org/10.1007/s12031-014-0319-2