Prion protein participates in the regulation of classical and alternative activation of BV2 microglia.
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 BV2 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.
State Key Laboratories for Agrobiotechnology, Key Lab of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing, China.
Fushan
F
Shi
Lifeng
L
Yang
Mohammed
M
Kouadir
Yang
Y
Yang
Tianjian
T
Ding
Jihong
J
Wang
Xiangmei
X
Zhou
Xiaomin
X
Yin
Deming
D
Zhao
D000818:Animals; D002460:Cell Line; D015536:Down-Regulation / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000166:cytology* / Q000502:physiology*; D009433:Neural Inhibition / Q000235:genetics; D018696:Neuroprotective Agents / Q000737:chemistry / Q000378:metabolism; D000072002:Prion Proteins; D011328:Prions / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics
D018696:Neuroprotective Agents; D000072002:Prion Proteins; D011328:Prions; C512657:Prnp protein, mouse; D034741:RNA, Small Interfering