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CpG-containing oligodeoxynucleotide promotes microglial cell uptake of amyloid β 1-42 peptide by up-regulating the expression of the G-protein-coupled receptor mFPR2

Laboratory of Molecular Immunoregulation, NCI-Frederick, Фредерик, Maryland, United States
The FASEB Journal (Impact Factor: 5.48). 01/2006; 19(14):2032-4. DOI: 10.1096/fj.05-4578fje
Source: PubMed

ABSTRACT Human G protein-coupled formyl peptide receptor like 1 (FPRL1) and its mouse homologue murine formyl peptide receptor 2 (mFPR2) mediate the chemotactic activity of amyloid beta 1-42 (Abeta42), a key pathogenic peptide in Alzheimer's disease (AD). Since mFPR2 is up-regulated in mouse microglia by lipopolysaccharide (LPS), a Toll-like receptor 4 ligand, we investigated the capacity of CpG-containing oligodeoxynucleotide (ODN), a Toll-like receptor (TLR) 9 ligand, to regulate the expression of mFPR2 in mouse microglia. CpG ODN markedly enhanced the expression and function of mFPR2 in microglial cells, which exhibited increased chemotactic responses to mFPR2 agonists, including Abeta42. The effect of CpG ODN is dependent on activation of p38 MAPK. Further studies showed that CpG ODN-treated microglia increased their capacity to endocytose Abeta42 through mFPR2, as this process was abrogated by pertussis toxin, a Gi protein inhibitor, and W peptide, another potent mFPR2 agonist. Our results suggest that TLR9 may play an important role in promoting microglial recognition of Abeta42, thus affecting the pathogenic process of AD.

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Available from: Jinyue Hu, Aug 08, 2015
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    • " PrP endocytosis . The GPCR FPRL1 is also involved in host defence against bacterial infection in the brain and in the clearance of damaged cells by monocyte - microglial cells ( Loitto et al . 2001 ; Le et al . 2002 ; Bergman et al . 2005 ) . In line with previous results using a human astrocytoma cell line and mouse microglia ( Le et al . 2000 ; Iribarren et al . 2005 ) , we could show here the expression of FPRL1 receptor by rat astrocytes and microglia ( Fig . 1 ) . This could be of particular interest , because it is known that the receptor interacts with a menagerie of structurally diverse Fig . 5 Quantitative analysis of PrP 106 – 126 uptake in glial cells and inhibition by the primary alcohol 1"
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