Branched-chain amino acids influence the immune properties of microglial cells and their responsiveness to pro-inflammatory signals

被引:107
作者
De Simone, Roberta [1 ]
Vissicchio, Federica [1 ]
Mingarelli, Cecilia [1 ]
De Nuccio, Chiara [1 ]
Visentin, Sergio [1 ]
Ajmone-Cat, Maria Antonietta [1 ]
Minghetti, Luisa [1 ]
机构
[1] Ist Super Sanita, Dept Cell Biol & Neurosci, Expt Neurol Unit, I-00161 Rome, Italy
来源
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE | 2013年 / 1832卷 / 05期
关键词
Brain macrophages; Microglial activation; M1; phenotype; M2; BCAA; Neurodegeneration; AMYOTROPHIC-LATERAL-SCLEROSIS; SYRUP-URINE-DISEASE; BRAIN-INJURY; METABOLISM; ACTIVATION; INHIBITION; RECEPTOR; LEUCINE; DOWNSTREAM; EXPRESSION;
D O I
10.1016/j.bbadis.2013.02.001
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The branched-chain amino acids (BCAAs) valine, leucine and isoleucine are essential amino acids involved in several important brain functions. Although commonly used as nutritional supplements, excessive intake of BCAAs might favour the establishment of neurotoxic conditions as indicated by the severe neurological symptoms characterising inherited disorders of BCAA catabolism such as maple syrup urine disease (MSUD). Recent evidence indicates that BCAAs induce excitotoxicity through mechanisms that require the presence of astrocytes. In the present study, we evaluated the effects of BCAAs on microglia, the main immune cells of the brain. As an experimental model we used primary microglial cells harvested from mixed glial cultures that had been kept in normal or high BCAA medium (H-BCAA). We show that H-BCAA microglial cells exhibit a peculiar phenotype characterized by a partial skewing toward the M2 state, with enhanced IL-10 expression and phagocytic activity but also increased free radical generation and decreased neuroprotective functions. We suggest that such an intermediate M1/M2 phenotype might result in a less efficient microglial response, which would promote the establishment of a low grade chronic inflammation and increase the likelihood of neurodegeneration. Although based on in vitro evidence, our study adds on to an increasing literature indicating that the increasing use of dietary integrators might deserve consideration for the possible drawbacks. In addition to excitotoxicity, the altered immune profile of microglia might represent a further mechanism by which BCAAs might turn into toxicants and facilitate neurodegeneration. (C) 2013 Elsevier B.V. All rights reserved.
引用
收藏
页码:650 / 659
页数:10
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