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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Manganese modulates pro-inflammatory gene expression in activated glia.
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Manganese modulates pro-inflammatory gene expression in activated glia.

机译：锰调节活化胶质细胞中促炎基因的表达。

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摘要

Redox-active metals are of paramount importance for biological functions. Their impact and cellular activities participate in the physiological and pathophysiological processes of the central nervous system (CNS), including inflammatory responses. Manganese is an essential trace element and it is required for normal biological activities and ubiquitous enzymatic reactions. However, excessive chronic exposure to manganese results in neurobehavioral deficits. Recent evidence suggests that manganese neurotoxicity involves activation of microglia or astrocytes, representative CNS immune cells. In this study, we assessed the molecular basis of the effects of manganese on the modulation of pro-inflammatory cytokines and nitric oxide (NO) production in primary rat cortical glial cells. Cultured glial cells consisted of 85% of astrocytes and 15% of microglia. Within the assayed concentrations, manganese was unable to induce tumor necrosis factor alpha (TNF-alpha) and inducible nitric oxide synthase (iNOS) expression, whereas it potentiated iNOS and TNF-alpha gene expression by lipopolysaccharide/interferon-gamma-activated glial cells. The enhancement was accompanied by elevation of free manganese, generation of oxidative stress, activation of mitogen-activated protein kinases, and increased NF-kappaB and AP-1 binding activities. The potentiated degradation of inhibitory molecule IkappaB-alpha was one of underlying mechanisms for the increased activation of NF-kappaB by manganese. However, manganese decreased iNOS enzymatic activity possibly through the depletion of cofactor since exogenous tetrahydrobiopterin reversed manganese's action. These data indicate that manganese could modulate glial inflammation through variable strategies.
机译：氧化还原活性金属对于生物学功能至关重要。它们的影响和细胞活动参与中枢神经系统（CNS）的生理和病理生理过程，包括炎症反应。锰是必不可少的微量元素，它是正常生物学活动和普遍存在的酶促反应所必需的。但是，长期过度暴露于锰会导致神经行为缺陷。最近的证据表明，锰的神经毒性涉及小胶质细胞或星形胶质细胞（代表中枢神经系统免疫细胞）的激活。在这项研究中，我们评估了锰对原代大鼠皮质神经胶质细胞促炎性细胞因子和一氧化氮（NO）产生的调节作用的分子基础。培养的神经胶质细胞由85％的星形胶质细胞和15％的小胶质细胞组成。在测定的浓度范围内，锰不能诱导肿瘤坏死因子α（TNF-α）和诱导型一氧化氮合酶（iNOS）表达，而锰通过脂多糖/干扰素-γ激活的神经胶质细胞增强iNOS和TNF-α基因表达。增强伴随着游离锰的升高，氧化应激的产生，促分裂原活化的蛋白激酶的活化以及NF-κB和AP-1结合活性的增加。抑制分子IkappaB-α的增强降解是锰增强NF-kappaB活化的基本机制之一。然而，由于外源四氢生物蝶呤逆转了锰的作用，锰可能通过辅助因子的消耗而降低了iNOS的酶活性。这些数据表明锰可以通过多种策略调节神经胶质炎症。

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