Effects of methylmercury on the secretion of pro-inflammatory cytokines from primary microglial cells and astrocytes
Effects of methylmercury on the secretion of pro-inflammatory cytokines from primary microglial cells and astrocytes
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DOI：
10.1016/j.neuro.2011.10.003
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发表时间：
2012-03-01
期刊：
影响因子：
3.4
通讯作者：
Chan, Hing Man
中科院分区：
文献类型：
--
作者：
Bassett, Tyler;Bach, Paxton;Chan, Hing Man
神经胶质细胞，包括少突胶质细胞、星形胶质细胞和小胶质细胞，对于中枢神经系统（CNS）的正常功能是重要的。特别是星形胶质细胞和小胶质细胞的CNS群体的失调或变化预计在许多神经退行性疾病中起作用，包括帕金森病、肌萎缩性侧索硬化症（ALS）和阿尔茨海默病（AD）。以往的研究报告甲基汞（甲基汞）诱导的神经胶质细胞功能的变化，然而，甲基汞对这些细胞的影响仍然知之甚少。本研究旨在探讨甲基汞对小胶质细胞和星形胶质细胞分泌促炎细胞因子的影响。还检查了小胶质细胞/星形胶质细胞比率对细胞因子分泌的影响。从新生BALB/C小鼠的脑中培养小胶质细胞和星形胶质细胞，给予甲基汞（0-1 μ M），并用PAM（3）CSK（4）（PAM（3））（一种Toll样受体（TLR）配体）刺激。此后，通过ELISA测量白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）和白细胞介素-1-β（IL-1 β）的分泌。甲基汞呈剂量依赖性地抑制IL-6的分泌，但对TNF-α的分泌无影响。在任何处理中均未观察到IL-1 β的变化，表明PAM（3）不能诱导神经胶质细胞分泌这种细胞因子。此外，小胶质细胞/星形胶质细胞的比例对IL-6的分泌有影响，但对TNF-α的分泌没有影响。这些结果表明，甲基汞可以改变神经胶质细胞的反应，与星形胶质细胞的相互作用可以影响培养的小胶质细胞的反应。这些结果对于了解甲基汞与神经退行性疾病的潜在关系以及解释未来使用单一培养物进行体外研究的结果具有重要意义。(C)2011 Elsevier Inc. All rights reserved.
Glial cells, including oligodendrocytes, astrocytes and microglia are important to proper central nervous system (CNS) function. Deregulation or changes to CNS populations of astrocytes and microglia in particular are expected to play a role in many neurodegenerative diseases, including Parkinson's disease, amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD). Previous studies have reported methylmercury (MeHg) induced changes in glial cell function; however, the effects of MeHg on these cells remains poorly understood. This study aims to examine the effect of MeHg on the secretion of proinflammatory cytokines from microglia and astrocytes. The impact of the microglia/astrocyte ratio on cytokine secretion was also examined. Microglia and astrocytes were cultured from the brains of neonatal BALB/C mice and dosed with MeHg (0-1 mu M) and stimulated with PAM(3)CSK(4) (PAM(3)), a toll-like receptor (TLR) ligand. After this, the secretion of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1-beta (IL-1 beta was measured by ELISA. MeHg reduced the secretion of IL-6 in a dose dependant manner but did not effect the secretion of TNF-a. No change in IL-1 beta was observed in any treatments, indicating that PAM(3) cannot induce the secretion of this cytokine from glial cells. Additionally, the ratio of microglia/astrocyte had an effect on the secretion of IL-6 but not TNF-alpha. These results indicate that MeHg can modify the response of glial cells and the interactions with astrocytes can affect the response of the microglia cells in culture. These results are significant in understanding the potential relationship with MeHg and neurodegenerative diseases and for the interpretation of results of future in vitro studies using monoculture. (C) 2011 Elsevier Inc. All rights reserved.