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Resveratrol reduces glutamate-mediated monocyte chemotactic protein-1 expression via inhibition of extracellular signal-regulated kinase 1/2 pathway in rat hippocampal slice cultures

Cited 31 time in Web of Science Cited 32 time in Scopus
Authors
Lee, Eun Ok; Park, Hee Ju; Kang, JiHee Lee; Kim, Hye-Sun; Chong, Young Hae
Issue Date
2010-03
Publisher
WILEY-BLACKWELL PUBLISHING, INC
Citation
JOURNAL OF NEUROCHEMISTRY; Vol.112 6; 1477-1488
Keywords
Alzheimer`s diseaseinterleukin-1 betaresveratrolmonocyte chemoattractant protein-1glutamateextracellular signal-regulated kinase 12
Abstract
Published evidence has linked glutamate with the pathogenesis of Alzheimer`s disease (AD) and the up-regulation of a variety of chemokines, including monocyte chemotactic protein-1 (MCP-1)/chemokine ligand 2, with AD-associated pathological changes. In this study, we assessed the potential molecular basis for the role of glutamate in hippocampal inflammation by determining its effects on MCP-1 induction. We also attempted to identify the mechanism by which resveratrol (trans-3,5,4`-trihydroxystilbene), a polyphenolic phytostilbene, modulates the expression of MCP-1 in the glutamate-stimulated hippocampus. An ex vivo study using rat hippocampal slices demonstrated a time- and dose-dependent increase in MCP-1 release from glutamate-exposed hippocampus. This increase was accompanied by enhanced MCP-1 gene expression via the activation of the MEK/extracellular signal-regulated kinase (ERK) pathway and interleukin-1 beta (IL-1 beta) expression. The inhibition of the MEK/ERK pathway with SL327, which is capable of crossing the blood-brain barrier, nearly abolished the observed glutamate-induced effects. Furthermore, anti-IL-1 beta antibodies suppressed the glutamate-induced expression of MCP-1 mRNA and protein, whereas an isotype-matched antibody exerted only minimal effects. It is worthy of note that resveratrol, to a similar degree as SL327, down-regulated glutamate-induced IL-1 beta expression and reduced the expression of MCP-1 mRNA and protein release via the inactivation of ERK1/2. These results indicate that the activation of the MEK/ERK pathway and the consequent IL-1 beta expression are essential for glutamate-stimulated MCP-1 production in the hippocampus. Additionally, our data reveal an anti-inflammatory mechanism of resveratrol involving the inactivation of the ERK1/2 pathway in the hippocampus, which is linked principally to AD-associated cognitive dysfunction.
ISSN
0022-3042
Language
English
URI
https://hdl.handle.net/10371/78088
DOI
https://doi.org/10.1111/j.1471-4159.2009.06564.x
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College of Medicine/School of Medicine (의과대학/대학원)Pharmacology (약리학전공)Journal Papers (저널논문_약리학전공)
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