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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
Author(s) -
Iribarren Pablo,
Chen Keqiang,
Hu Jinyue,
Gong Wanghua,
Cho Edward H.,
Lockert Stephen,
Uranchimeg Badarch,
Wang Ji Ming
Publication year - 2005
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.05-4578fje
Subject(s) - microglia , pertussis toxin , receptor , cpg oligodeoxynucleotide , microbiology and biotechnology , tlr9 , peptide , toll like receptor , p38 mitogen activated protein kinases , formyl peptide receptor , chemistry , lipopolysaccharide , agonist , chemotaxis , biology , mapk/erk pathway , innate immune system , immunology , g protein , signal transduction , inflammation , biochemistry , gene expression , gene , dna methylation
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 β 1–42 (Aβ 42 ), 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 Aβ 42 . 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 Aβ 42 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 Aβ 42 , thus affecting the pathogenic process of AD.