首页> 外文期刊>Journal of Neuroimmunology: Official Bulletin of the Research Committee on Neuroimmunology of the World Federation of Neurology >Systemic treatment with the inhibitory neurotransmitter gamma-aminobutyric acid aggravates experimental autoimmune encephalomyelitis by affecting proinflammatory immune responses
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Systemic treatment with the inhibitory neurotransmitter gamma-aminobutyric acid aggravates experimental autoimmune encephalomyelitis by affecting proinflammatory immune responses

机译:抑制性神经递质γ-氨基丁酸的全身性治疗通过影响促炎性免疫反应,加重了实验性自身免疫性脑脊髓炎

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摘要

Transcriptomic and proteomic analyses of multiple sclerosis (MS) lesions indicate alterations in the gamma-aminobutyric acid (GABA) inhibitory system, suggesting its involvement in the disease process. To further elucidate the role of GABA in central nervous system (CNS) inflammation in vivo, the chronic myelin oligodendrocyte glycoprotein (MOG)35-55 experimental autoimmune encephalomyelitis (EAE) model was used. Daily GABA injections (200mg/kg) from day 3 onwards significantly augmented disease severity, which was associated with increased CNS mRNA expression levels of tumor necrosis factor alpha (TNF-??) and interleukin (IL)-6. GABA-treated mice showed enhanced MOG-dependent proliferation and were skewed towards a T helper 1 phenotype. Moreover, in vitro, the lipopolysaccharide (LPS)-induced increase in interleukin (IL)-6 production by macrophages was enhanced at low GABA concentrations (0.03-0.3mM). In sharp contrast to exogenous GABA administration, endogenous GABA increment by systemic treatment with the GABA-transaminase inhibitor vigabatrin (250mg/kg) had prophylactic as well as therapeutic potential in EAE. Together, these results indicate an immune amplifying role of GABA in neuroinflammatory diseases like MS. ? 2012 Elsevier B.V.
机译:对多发性硬化症(MS)病变的转录组学和蛋白质组学分析表明,γ-氨基丁酸(GABA)抑制系统发生了变化,表明其参与了疾病过程。为了进一步阐明GABA在体内中枢神经系统(CNS)炎症中的作用,使用了慢性髓磷脂少突胶质细胞糖蛋白(MOG)35-55实验性自身免疫性脑脊髓炎(EAE)模型。从第3天开始每天注射GABA(200mg / kg)显着增加疾病的严重性,这与肿瘤坏死因子α(TNF-α)和白介素(IL)-6的CNS mRNA表达水平增加有关。用GABA处理的小鼠表现出增强的MOG依赖性增殖,并且偏向T辅助1表型。此外,在体外,在低GABA浓度(0.03-0.3mM)下,巨噬细胞引起的脂多糖(LPS)诱导的白介素(IL)-6产量增加。与外源性GABA形成鲜明对比的是,通过GABA转氨酶抑制剂vigabatrin(250mg / kg)的全身治疗,内源性GABA的增加在EAE中具有预防和治疗的潜力。总之,这些结果表明,GABA在神经发炎性疾病(如MS)中具有免疫放大作用。 ? 2012年Elsevier B.V.

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