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 >Inhibition of cytokine-inducible nitric oxide synthase in rat microglia and murine macrophages by methyl-2,5-dihydroxycinnamate.
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Inhibition of cytokine-inducible nitric oxide synthase in rat microglia and murine macrophages by methyl-2,5-dihydroxycinnamate.

机译:2,5-二羟基肉桂酸甲酯对大鼠小胶质细胞和鼠巨噬细胞中细胞因子诱导型一氧化氮合酶的抑制作用。

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摘要

Microglial cells are resident macrophages in the central nervous system (CNS) which serve specific functions in the defence of the CNS against microorganisms, the removal of tissue debris in neurodegenerative diseases or during normal development, and in autoimmune inflammatory disorders of the brain. Microglia express a cytokine-inducible isoform of nitric oxide synthase, which leads to the production of nitric oxide (NO). Since NO is highly toxic to neurons and oligodendrocytes, we were interested to test down-regulating neuropeptides and second messenger de-activators in order to identify novel antagonists of cytokine-induced NO production. We found that only the tyrosine kinase inhibitor methyl-2,5-dihydroxycinnamate suppressed cytokine-induced NO production by rat microglial cells and murine macrophages, while a range of other tyrosine kinase inhibitors, neuropeptides and growth factors was ineffective. Since NO production may play a role in the pathogenesis of experimental neuro-immunological disorders like experimental autoimmune encephalomyelitis and experimental autoimmune neuritis, our findings suggest a possible therapeutic role for tyrosine kinase inhibitors.
机译:小胶质细胞是中枢神经系统(CNS)中的常驻巨噬细胞,在中枢神经系统防御微生物,清除神经退行性疾病或正常发育过程中的组织碎屑以及大脑自身免疫性炎性疾病中起特定作用。小胶质细胞表达一氧化氮合酶的细胞因子诱导型亚型,这导致一氧化氮(NO)的产生。由于NO对神经元和少突胶质细胞有剧毒,因此我们有兴趣测试下调的神经肽和第二信使去激活剂,以鉴定细胞因子诱导的NO产生的新型拮抗剂。我们发现只有酪氨酸激酶抑制剂-2,5-二羟基肉桂酸甲酯抑制细胞因子诱导的大鼠小胶质细胞和鼠巨噬细胞产生NO,而其他一系列酪氨酸激酶抑制剂,神经肽和生长因子无效。由于NO的产生可能在实验性神经免疫疾病(例如实验性自身免疫性脑脊髓炎和实验性自身免疫性神经炎)的发病机理中起作用,因此我们的发现表明酪氨酸激酶抑制剂可能具有治疗作用。

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