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Prion protein participates in the regulation of classical and alternative activation of BV 2 microglia
Author(s) -
Shi Fushan,
Yang Lifeng,
Kouadir Mohammed,
Yang Yang,
Ding Tianjian,
Wang Jihong,
Zhou Xiangmei,
Yin Xiaomin,
Zhao Deming
Publication year - 2013
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12053
Subject(s) - microglia , prnp , neuroprotection , microbiology and biotechnology , biology , gene silencing , proinflammatory cytokine , messenger rna , context (archaeology) , immunology , neuroscience , inflammation , biochemistry , gene , paleontology , allele
The cellular prion protein ( PrP C ) is a glycoprotein anchored by glycosylphosphatidylinositol ( GPI ) to the cell surface and is abundantly expressed in the central nervous system. Numerous studies have suggested a protective function for PrP C , including protection from ischemic and excitotoxic lesions and several apoptotic insults, and recent reports have shown that PrP C has a context‐dependent neuroprotective function. In this study, we investigated the effect of PPNP down‐regulation on various forms of microglial activation. We first examined the mRNA expression of PRNP upon exposure to IFN ‐γ, IL‐4, or IL‐10 in BV 2 microglia. We then analyzed the effect of si‐ RNA ‐mediated disruption of PRNP on different parameters of microglial activation in IFN ‐γ‐, IL‐4‐, or IL‐10‐stimulated microglia. The results showed that PRNP mRNA expression was invariably down‐regulated in microglia upon exposure to IFN ‐γ, IL‐4, or IL‐10. PRNP silencing prior to cytokines treatment reduced the responsiveness of microglia to INF ‐γ treatment, significantly altered IL‐4‐induced microglial activation phenotype, and had no effect on IL‐10‐induced microglial activation. Together, these results support a role of PrP C in the modulation of the shift of microglia from a quiescent state to an activated phenotype and in the regulation of the microglial response during classical and alternative activation.