Atorvastatin prevents age-related and amyloid-beta-induced microglial activation by blocking interferon-gamma release from natural killer cells in the brain
Citation:
Lyons A, Murphy KJ, Clarke R, Lynch MA, Atorvastatin prevents age-related and amyloid-beta-induced microglial activation by blocking interferon-gamma release from natural killer cells in the brain, Journal of Neuroinflammation, 8, 27, 2011Download Item:
Atorvastatin prevents age-related and amyloid-?-induced microglial activation by blocking interferon-? release from natural killer cells in the brain.pdf (Published (publisher's copy) - Peer Reviewed) 494.6Kb
Abstract:
Abstract: Background: Microglial function is modulated by several factors reflecting the numerous receptors expressed on the cell surface, however endogenous factors which contribute to the age-related increase in microglial activation remain largely unknown. One possible factor which may contribute is interferon-gamma (IFN gamma). IFN gamma has been shown to increase in the aged brain and potently activates microglia, although its endogenous cell source in the brain remains unidentified.
Methods: Male Wistar rats were used to assess the effect of age and amyloid-beta (A beta) on NK cell infiltration into the brain. The effect of the anti-inflammatory compound, atorvastatin was also assessed under these conditions. We measured cytokine and chemokine (IFN gamma, IL-2, monocyte chemoattractant protein-1 (MCP-1) and IFN gamma-induced protein 10 kDa (IP-10)), expression in the brain by appropriate methods. We also looked at NK cell markers, CD161, NKp30 and NKp46 using flow cytometry and western blot.
Results: Natural killer (NK) cells are a major source of IFN gamma in the periphery and here we report the presence of CD161(+) NKp30(+) cells and expression of CD161 and NKp46 in the brain of aged and Ab-treated rats. Furthermore, we demonstrate that isolated CD161(+) cells respond to interleukin-2 (IL-2) by releasing IFN gamma. Atorvastatin, the HMG-CoA reductase inhibitor, attenuates the increase in CD161 and NKp46 observed in hippocampus of aged and A beta-treated rats. This was paralleled by a decrease in IFNg, markers of microglial activation and the chemokines, MCP-1 and IP-10 which are chemotactic for NK cells.
Conclusions: We propose that NK cells contribute to the age-related and A beta-induced neuroinflammatory changes and demonstrate that these changes can be modulated by atorvastatin treatment.
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Health Research Board (HRB)
Higher Education Authority (HEA)
Science Foundation Ireland (SFI)
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http://people.tcd.ie/lynchmaDescription:
PUBLISHED
Author: LYONS, ANTHONY; LYNCH, MARINA
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Journal of Neuroinflammation8
27
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Immunology, COA REDUCTASE INHIBITORSubject (TCD):
Immunology, Inflammation & InfectionDOI:
http://dx.doi.org/10.1186/1742-2094-8-27ISSN:
1742-2094Licences: