Luteolin inhibits cytokine expression in endotoxin/cytokine-stimulated microglia
Luteolin inhibits cytokine expression in endotoxin/cytokine-stimulated microglia
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DOI：
10.1016/j.jnutbio.2010.01.011
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发表时间：
2011-07-01
影响因子：
5.6
通讯作者：
Chen, Chun-Jung
中科院分区：
文献类型：
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作者：
Kao, Tsung-Kuei;Ou, Yen-Chuan;Chen, Chun-Jung
小胶质细胞激活通过产生过多的促炎细胞因子和一氧化氮（NO）在神经退行性疾病的发病机制中起关键作用。木犀草素是一种天然存在的多酚类黄酮抗氧化剂，在体外和体内都具有有效的抗炎和神经保护作用。然而，木犀草素介导的小胶质细胞免疫调节的分子机制尚不完全清楚。在本研究中，我们报道了木犀草素对大鼠初级小胶质细胞和BV-2小胶质细胞中脂多糖(LPS)/干扰素γ (ifn - γ)诱导的NO和促炎细胞因子产生的抑制作用。木犀草素浓度依赖性地抑制LPS/ ifn - γ诱导的NO、肿瘤坏死因子α (tnf - α)和白细胞介素1 β (IL-1 β)的产生以及诱导型一氧化氮合酶（iNOS）蛋白和mRNA的表达。木犀草素对LPS/ ifn - γ激活的BV-2小胶质细胞中核因子κ B （nf - κ B）、转录信号传导和激活因子1 （STAT1）、干扰素调节因子1 （IRF-1）等转录因子活性有抑制作用。生化和药理学研究发现木草素的抗炎作用伴随着下调细胞外信号调节激酶（ERK）、p38、c-Jun n-末端激酶（JNK）。Akt和Src。进一步的研究表明木犀草素对细胞内信号执行和促炎细胞因子表达的抑制作用与氧化应激的解决和蛋白磷酸酶活性的促进有关。总之，这些结果表明木犀草素抑制nf - κ B、STAT1和IRF-1信号，从而减弱脑小胶质细胞的炎症反应。(C) 2011爱思唯尔公司版权所有。
Microglial activation plays a pivotal role in the pathogenesis of neurodegenerative disease by producing excessive proinflammatory cytokines and nitric oxide (NO). Luteolin, a naturally occurring polyphenolic flavonoid antioxidant, has potent anti-inflammatory and neuroprotective properties both in vitro and in vivo. However, the molecular mechanism of luteolin-mediated immune modulation in microglia is not fully understood. In the present study, we report the inhibitory effect of luteolin on lipopolysaccharide (LPS)/interferon gamma (IFN-gamma)-induced NO and proinflammatory cytokine production in rat primary microglia and BV-2 microglial cells. Luteolin concentration-dependently abolished LPS/IFN-gamma-induced NO, tumor necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL-1 beta) production as well as inducible nitric oxide synthase (iNOS) protein and mRNA expression. Luteolin exerted an inhibitory effect on transcription factor activity including nuclear factor kappa B (NF-kappa B), signal transducer and activator of transcription 1 (STAT1) and interferon regulatory factor 1 (IRF-1) in LPS/IFN-gamma-activated BV-2 microglial cells. Biochemical and pharmacological studies revealed that the anti-inflammatory effect of luteolin was accompanied by down-regulation of extracellular signal-regulated kinase (ERK), p38, c-Jun N-terminal kinase (JNK). Akt and Src. Further studies have demonstrated that the inhibitory effect of luteolin on intracellular signaling execution and proinflammatory cytokine expression is associated with resolution of oxidative stress and promotion of protein phosphatase activity. Together, these results suggest that luteolin suppresses NF-kappa B, STAT1 and IRF-1 signaling, thus attenuating inflammatory response of brain microglial cells. (C) 2011 Elsevier Inc. All rights reserved.