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The Soluble Form of the Cellular Prion Protein Enhances Phagocytic Activity and Cytokine Production by Human Monocytes Via Activation of ERK and $NF-{\kappa}B$

  • Jeon, Jae-Won (Aging Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Park, Bum-Chan (Aging Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Jung, Joon-Goo (Aging Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Jang, Young-Soon (Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST) ;
  • Shin, Eui-Cheol (Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST) ;
  • Park, Young Woo (Aging Research Center, Korea Research Institute of Bioscience and Biotechnology)
  • Received : 2013.07.09
  • Accepted : 2013.07.22
  • Published : 2013.08.30
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Abstract

The $PrP^C$ is expressed in many types of immune cells including monocytes and macrophages, however, its function in immune regulation remains to be elucidated. In the present study, we examined a role for $PrP^C$ in regulation of monocyte function. Specifically, the effect of a soluble form of $PrP^C$ was studied in human monocytes. A recombinant fusion protein of soluble human $PrP^C$ fused with the Fc portion of human IgG1 (designated as soluble $PrP^C$-Fc) bound to the cell surface of monocytes, induced differentiation to macrophage-like cells, and enhanced adherence and phagocytic activity. In addition, soluble $PrP^C$-Fc stimulated monocytes to produce pro-inflammatory cytokines such as $TNF-{\alpha}$, $IL-1{\beta}$, and IL-6. Both ERK and $NF-{\kappa}B$ signaling pathways were activated in soluble $PrP^C$-treated monocytes, and inhibitors of either pathway abrogated monocyte adherence and cytokine production. Taken together, we conclude that soluble $PrP^C$-Fc enhanced adherence, phagocytosis, and cytokine production of monocytes via activation of the ERK and $NF-{\kappa}B$ signaling pathways.

Keywords

References

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