Anti-inflammatory effects of the neurotransmitter agonist Honokiol in a mouse model of allergic asthma.
Anti-inflammatory effects of the neurotransmitter agonist Honokiol in a mouse model of allergic asthma.
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DOI：
10.4049/jimmunol.1000630
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发表时间：
2010-11-01
期刊：
影响因子：
--
通讯作者：
Bishop GA
中科院分区：
文献类型：
--
作者：
Munroe ME;Businga TR;Kline JN;Bishop GA
慢性气道炎症是哮喘的标志，哮喘是一种具有巨大社会影响的免疫性疾病。Honokaline（HNK）是一种从甘草中纯化的酚类神经递质受体（GABAA）激动剂，具有抗炎特性，包括稳定实验诱导的关节炎中的炎症。本研究验证了HNK可以抑制过敏性哮喘的慢性炎症成分的预测。与未经处理的对照组相比，对卵清蛋白（OVA）致敏并激发的C57 Bl/6小鼠对乙酰甲胆碱激发的气道高反应性和嗜酸性粒细胞增多症增加。HNK处理的小鼠显示气道高反应性降低以及肺嗜酸性粒细胞增多症显著降低。组织学研究显示HNK治疗后肺部炎症、杯状细胞增生和胶原沉积显著下降。HNK处理小鼠的抗原回忆反应显示，尽管Th 2型细胞因子增加，但对OVA的促炎细胞因子（包括TNF-α、IL-6、Th 1和Th 17型细胞因子）减少。调节性细胞因子IL-10和TGF-β也增加。肺匀浆的评估揭示了类似的细胞因子模式，肺中FoxP 3+细胞的数量显著增加。HNK能够以GABAA依赖性方式改变B-和T-淋巴细胞细胞因子分泌。这些结果表明，即使在Th 2细胞因子增加的情况下，哮喘的症状和病理也可以得到缓解，并且神经递质激动剂如HNK有望作为一类新型的治疗慢性哮喘的抗炎剂。
Chronic airway inflammation is a hallmark of asthma, an immune-based disease with great societal impact. Honokiol (HNK), a phenolic neurotransmitter receptor (GABAA) agonist purified from magnolia, has anti-inflammatory properties, including stabilization of inflammation in experimentally-induced arthritis. The present study tested the prediction that HNK could inhibit the chronic inflammatory component of allergic asthma. C57Bl/6 mice sensitized to and challenged with ovalbumin (OVA) had increased airway hyperresponsiveness to methacholine challenge and eosinophilia compared to naïve controls. HNK-treated mice showed a reduction in airway hyperresponsiveness as well as a significant decrease in lung eosinophilia. Histopathology studies revealed a marked drop in lung inflammation, goblet cell hyperplasia, and collagen deposition with HNK treatment. Antigen recall responses from HNK-treated mice showed decreased pro-inflammatory cytokines in response to OVA, including TNF-α, IL-6, Th1, and Th17-type cytokines, despite an increase in Th2-type cytokines. Regulatory cytokines IL-10 and TGF-β were also increased. Assessment of lung homogenates revealed a similar pattern of cytokines, with a noted increase in the number of FoxP3+ cells in the lung. HNK was able to alter B- and T-lymphocyte cytokine secretion in a GABAA dependent manner. These results indicate that symptoms and pathology of asthma can be alleviated even in the presence of increased Th2 cytokines, and that neurotransmitter agonists such as HNK have promise as a novel class of antiinflammatory agents in the treatment of chronic asthma.
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DOI：
10.1084/jem.193.8.943
发表时间：
2001-04-16
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Brown KD;Hostager BS;Bishop GA
通讯作者：
Bishop GA
影响因子：
3.1
作者：
Ai, JL;Wang, XM;Nielsen, M
通讯作者：
Nielsen, M
影响因子：
4.8
作者：
Chen, Y;Thai, P;Wu, R
通讯作者：
Wu, R
影响因子：
5.4
作者：
BISHOP, GA;WARREN, WD;BERTON, MT
通讯作者：
BERTON, MT
影响因子：
5.8
作者：
Durairaj, L;Launspach, J;Zabner, J
通讯作者：
Zabner, J