PMID- 21453520
OWN - NLM
STAT- MEDLINE
DCOM- 20110722
LR  - 20211020
IS  - 1742-2094 (Electronic)
IS  - 1742-2094 (Linking)
VI  - 8
DP  - 2011 Mar 31
TI  - Atorvastatin prevents age-related and amyloid-beta-induced microglial activation by 
      blocking interferon-gamma release from natural killer cells in the brain.
PG  - 27
LID - 10.1186/1742-2094-8-27 [doi]
AB  - 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 (IFNgamma). 
      IFNgamma 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 
      (Abeta) 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 (IFNgamma, IL-2, monocyte chemoattractant protein-1 (MCP-1) 
      and IFNgamma-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 IFNgamma 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 Abeta-treated rats. 
      Furthermore, we demonstrate that isolated CD161+ cells respond to interleukin-2 
      (IL-2) by releasing IFNgamma. Atorvastatin, the HMG-CoA reductase inhibitor, 
      attenuates the increase in CD161 and NKp46 observed in hippocampus of aged and 
      Abeta-treated rats. This was paralleled by a decrease in IFNgamma, 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 
      Abeta-induced neuroinflammatory changes and demonstrate that these changes can be 
      modulated by atorvastatin treatment.
FAU - Lyons, Anthony
AU  - Lyons A
AD  - Physiology Department, Trinity College Institute for Neuroscience, Trinity 
      College, Dublin 2, Ireland. lyonsan@tcd.ie
FAU - Murphy, Kevin J
AU  - Murphy KJ
FAU - Clarke, Rachael
AU  - Clarke R
FAU - Lynch, Marina A
AU  - Lynch MA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110331
PL  - England
TA  - J Neuroinflammation
JT  - Journal of neuroinflammation
JID - 101222974
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Anticholesteremic Agents)
RN  - 0 (Biomarkers)
RN  - 0 (Heptanoic Acids)
RN  - 0 (NK Cell Lectin-Like Receptor Subfamily B)
RN  - 0 (Natural Cytotoxicity Triggering Receptor 1)
RN  - 0 (Pyrroles)
RN  - 82115-62-6 (Interferon-gamma)
RN  - A0JWA85V8F (Atorvastatin)
SB  - IM
MH  - Aging/*physiology
MH  - Amyloid beta-Peptides/*metabolism
MH  - Animals
MH  - Anticholesteremic Agents/pharmacology
MH  - Atorvastatin
MH  - Biomarkers/metabolism
MH  - Brain/cytology/metabolism
MH  - Heptanoic Acids/*pharmacology
MH  - Interferon-gamma/*metabolism
MH  - Killer Cells, Natural/cytology/*drug effects/*metabolism
MH  - Male
MH  - Microglia/cytology/*metabolism
MH  - NK Cell Lectin-Like Receptor Subfamily B/metabolism
MH  - Natural Cytotoxicity Triggering Receptor 1/metabolism
MH  - Pyrroles/*pharmacology
MH  - Rats
MH  - Rats, Wistar
PMC - PMC3077319
EDAT- 2011/04/02 06:00
MHDA- 2011/07/23 06:00
PMCR- 2011/03/31
CRDT- 2011/04/02 06:00
PHST- 2011/01/12 00:00 [received]
PHST- 2011/03/31 00:00 [accepted]
PHST- 2011/04/02 06:00 [entrez]
PHST- 2011/04/02 06:00 [pubmed]
PHST- 2011/07/23 06:00 [medline]
PHST- 2011/03/31 00:00 [pmc-release]
AID - 1742-2094-8-27 [pii]
AID - 10.1186/1742-2094-8-27 [doi]
PST - epublish
SO  - J Neuroinflammation. 2011 Mar 31;8:27. doi: 10.1186/1742-2094-8-27.