Amyloid-β peptides induce several chemokine mRNA expressions in the primary microglia and Ra2 cell line via the PI3K/Akt and/or ERK pathway

Department of Immunology, Nagoya University Graduate School of Medicine, 65 Turumai-cho, Showa-ku, Nagoya, Aichi 466-8520, Japan.
Neuroscience Research (Impact Factor: 2.15). 12/2006; 56(3):294-9. DOI: 10.1016/j.neures.2006.07.009
Source: PubMed

ABSTRACT Alzheimer's disease (AD) is characterized by the presence of senile plaques composed primarily of amyloid-beta peptide (Abeta) in the brain. Microglia have been reported to surround these Abeta plaques, which have opposite roles, provoking a microglia-mediated inflammatory response that contributes to neuronal cell loss or the removal of Abeta and damaged neurons. To perform these tasks microglia migrate to the sites of Abeta secretion. We herein analyzed the process of chemokine expression induced by Abeta stimulation in primary murine microglia and Ra2 microglial cell line. We found that Abeta1-42 induced the expressions of CCL7, CCL2, CCL3, CCL4 and CXCL2 in the microglia. The signal transduction pathway for the expression of CCL2 and CCL7 mRNA induced by Abeta1-42 was found to depend on phosphatidylinositol 3-kinase (PI3K)/Akt and extracellular signal-regulated kinase (ERK), whereas the pathway for CCL4 depended only on PI3K/Akt. These inflammatory chemokine expressions by Abeta stimulation emphasize the contribution of neuroinflammatory mechanisms to the pathogenesis of AD.

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    • "The distribution of microglia is regulated by over-expressing CCL2 or genetically ablation of CCL2 receptor in APP transgenic mice (El Khoury et al., 2007; Yamamoto et al., 2005). Furthermore, mRNA levels of several chemokines in microglia are upregulated by aggregated Ab (Ito et al., 2006). Previous in vitro studies have suggested that the uptake of aggregated Ab by microglia is mediated by scavenger receptors, integrin, and formyl peptide like receptor 1 (FPRL1) (El Khoury et al., 1996; Koenigsknecht and Landreth, 2004; Lorton et al., 2000). "
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