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
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.
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TLR 2, 4, and 9 signaling modulates phagocytosis and clearance of neurotoxic amyloid deposition in neurodegenerative diseases, perhaps by MyD88 independent signaling pathways.
“It has also been reported by others that TLR 2, 4, and 9 signaling modulates phacogytosis and clearance of neurotoxic amyloid deposition in neurodegenerative diseases, perhaps by MyD88 independent signaling pathways [43], [55].”
From MicroRNA 146a (miR-146a) Is Over-Expressed during Prion Disease and Modulates the Innate Immune Response and the Microglial Activation State (2012) · cites this paper as [43]
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- Authors
- Iribarren, P., Chen, K., Hu, J., Gong, W., Cho, E. H., Lockert, S., Uranchimeg, B., & Wang, J. M.
- Affiliations
- Laboratory of Molecular Immunoregulation Center for Cancer Research National Cancer Institute at Frederick Frederick Maryland 21702 USA
- Basic Research Program SAIC‐Frederick Frederick Maryland 21702 USA
- Image Analysis Laboratory SAIC‐Frederick Frederick Maryland 21702 USA
- Developmental Therapeutics Program Tumor Hypoxia Laboratory SAIC‐Frederick Frederick Maryland 21702 USA
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2005-10-11
- Volume
- 19
- Issue
- 14
- Pages
- 2032-2034
- ISSN
- 0892-6638
- 1530-6860
- Cited by
- 73
- References
- 7
- Language
- en
- Funders
- National Cancer Institute
- National Institutes of Health
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