title: The Soluble Form of the Cellular Prion Protein Enhances Phagocytic Activity and Cytokine Production by Human Monocytes Via Activation of ERK and NF-κB.
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-α, IL-1β, and IL-6. Both ERK and NF-κB 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-κB signaling pathways.
authors.affiliation: Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Korea.
authors.forename: Jae-Won
authors.initials: JW
authors.lastname: Jeon
authors.forename: Bum-Chan
authors.initials: BC
authors.lastname: Park
authors.forename: Joon-Goo
authors.initials: JG
authors.lastname: Jung
authors.forename: Young-Soon
authors.initials: YS
authors.lastname: Jang
authors.forename: Eui-Cheol
authors.initials: EC
authors.lastname: Shin
authors.forename: Young Woo
authors.initials: YW
authors.lastname: Park
keywords: Adherence; Phagocytosis; Pro-inflammatory cytokine; Signaling; Soluble PrPC