PMID- 15890528
OWN - NLM
STAT- MEDLINE
DCOM- 20050829
LR  - 20211109
IS  - 1044-7431 (Print)
IS  - 1044-7431 (Linking)
VI  - 29
IP  - 3
DP  - 2005 Jul
TI  - Activation of microglia by aggregated beta-amyloid or lipopolysaccharide impairs 
      MHC-II expression and renders them cytotoxic whereas IFN-gamma and IL-4 render 
      them protective.
PG  - 381-93
AB  - 'Protective autoimmunity' refers to a well-controlled anti-self response that 
      helps the body resist neurodegeneration. The response is mediated by autoimmune T 
      cells, which produce cytokines and growth factors. Using an in vitro assay of 
      hippocampal slices, we show that the cytokines interferon-gamma and (especially) 
      interleukin-4, characteristic of pro-inflammatory and anti-inflammatory T cells, 
      respectively, can make microglia neuroprotective. Aggregated beta-amyloid, like 
      bacterial cell wall-derived lipopolysaccharide, rendered the microglia cytotoxic. 
      Cytotoxicity was correlated with a signal transduction pathway that 
      down-regulates expression of class-II major histocompatibility proteins (MHC-II) 
      through the MHC-II-transactivator and the invariant chain. Protection by 
      interleukin-4 was attributed to down-regulation of tumor necrosis factor-alpha 
      and up-regulation of insulin-like growth factor I. These findings suggest that 
      beneficial or harmful expression of the local immune response in the damaged CNS 
      depends on how microglia interpret the threat, and that a well-regulated 
      T-cell-mediated response enables microglia to alleviate rather than exacerbate 
      stressful situations in the CNS.
FAU - Butovsky, Oleg
AU  - Butovsky O
AD  - Department of Neurobiology, The Weizmann Institute of Science, 76100 Rehovot, 
      Israel.
FAU - Talpalar, Adolfo E
AU  - Talpalar AE
FAU - Ben-Yaakov, Keren
AU  - Ben-Yaakov K
FAU - Schwartz, Michal
AU  - Schwartz M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Cell Neurosci
JT  - Molecular and cellular neurosciences
JID - 9100095
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 207137-56-2 (Interleukin-4)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Amyloid beta-Peptides/antagonists & inhibitors/immunology/pharmacology
MH  - Animals
MH  - Animals, Newborn
MH  - Autoimmunity/drug effects/immunology
MH  - Cell Line
MH  - Cells, Cultured
MH  - Down-Regulation/drug effects/immunology
MH  - Encephalitis/*immunology/physiopathology/therapy
MH  - Gliosis/*immunology/physiopathology/therapy
MH  - Hippocampus/drug effects/immunology/physiopathology
MH  - Histocompatibility Antigens Class II/drug effects/*immunology
MH  - Insulin-Like Growth Factor I/drug effects/immunology
MH  - Interferon-gamma/*immunology/pharmacology
MH  - Interleukin-4/*immunology/pharmacology
MH  - Lipopolysaccharides/antagonists & inhibitors/immunology/pharmacology
MH  - Lymphocyte Activation/drug effects/immunology
MH  - Microglia/drug effects/*immunology
MH  - Neurodegenerative Diseases/immunology/physiopathology/therapy
MH  - Organ Culture Techniques
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - T-Lymphocytes/drug effects/immunology
MH  - Transcriptional Activation/drug effects/physiology
MH  - Tumor Necrosis Factor-alpha/drug effects/immunology
EDAT- 2005/05/14 09:00
MHDA- 2005/08/30 09:00
CRDT- 2005/05/14 09:00
PHST- 2004/09/19 00:00 [received]
PHST- 2005/03/13 00:00 [revised]
PHST- 2005/03/15 00:00 [accepted]
PHST- 2005/05/14 09:00 [pubmed]
PHST- 2005/08/30 09:00 [medline]
PHST- 2005/05/14 09:00 [entrez]
AID - S1044-7431(05)00056-4 [pii]
AID - 10.1016/j.mcn.2005.03.005 [doi]
PST - ppublish
SO  - Mol Cell Neurosci. 2005 Jul;29(3):381-93. doi: 10.1016/j.mcn.2005.03.005.