Sustained sensitizing effects of tumor necrosis factor alpha on sensory nerves in lung and airways.
Sustained sensitizing effects of tumor necrosis factor alpha on sensory nerves in lung and airways.
复制标题
DOI：
10.1016/j.pupt.2017.06.001
复制
发表时间：
2017-12
影响因子：
3.2
通讯作者：
Lee LY
中科院分区：
文献类型：
--
作者：
Lin RL;Gu Q;Khosravi M;Lee LY
肿瘤坏死因子α（tumor necrosis factor alpha，TNFα）在气道炎症性疾病的发病机制中起重要作用。在健康人受试者中，吸入雾化TNFα诱导气道高反应性并伴有气道炎症，但其潜在机制尚未完全了解。我们最近报道了一系列研究，旨在研究TNFα是否能提高小鼠模型迷走支气管感觉神经的敏感性;这些研究在此简要综述中进行了总结。我们的研究结果表明，肺内滴注TNFα 24小时后诱导明显的气道炎症，表现为肺和气道中嗜酸性粒细胞和中性粒细胞的浸润以及炎症介质和细胞因子的释放。伴随着这些炎症反应，迷走神经肺C-纤维和沉默的快速适应受体对辣椒素的敏感性在TNFα处理后显著升高，辣椒素是瞬时受体电位香草酸1型受体的选择性激动剂。在分离的肺感觉神经元中也观察到TNFα诱导的对辣椒素的敏感性的明显增加，这表明敏化作用主要通过TNFα对这些神经元的直接作用介导。此外，相同的TNFα治疗也诱导了清醒小鼠对NH3吸入激发的持续（> 7天）咳嗽高反应性。在TNF受体双纯合突变小鼠中，TNFα治疗引起的气道炎症和对肺感觉神经元的增敏作用均被消除，表明TNF受体活化参与其中。这些结果表明，TNFα诱导的迷走支气管肺纤维传入的超敏性可能是健康个体吸入TNFα引起的气道高反应性的部分原因。
Tumor necrosis factor alpha (TNFα) plays a significant role in the pathogenesis of airway inflammatory diseases. Inhalation of aerosolized TNFα induced airway hyperresponsiveness accompanied by airway inflammation in healthy human subjects, but the underlying mechanism is not fully understood. We recently reported a series of studies aimed to investigate if TNFα elevates the sensitivity of vagal bronchopulmonary sensory nerves in a mouse model; these studies are summarized in this mini-review. Our results showed that intratracheal instillation of TNFα induced pronounced airway inflammation 24 hours later, as illustrated by infiltration of eosinophils and neutrophils and the release of inflammatory mediators and cytokines in the lung and airways. Accompanying these inflammatory reactions, the sensitivity of vagal pulmonary C-fibers and silent rapidly adapting receptors to capsaicin, a selective agonist of transient receptor potential vanilloid type 1 receptor, was markedly elevated after the TNFα treatment. A distinct increase in the sensitivity to capsaicin induced by TNFα was also observed in isolated pulmonary sensory neurons, suggesting that the sensitizing effect is mediated primarily through a direct action of TNFα on these neurons. Furthermore, the same TNFα treatment also induced a lingering (> 7days) cough hyperresponsiveness to inhalation challenge of NH3 in awake mice. Both the airway inflammation and the sensitizing effect on pulmonary sensory neurons caused by the TNFα treatment were abolished in the TNF-receptor double homozygous mutant mice, indicating the involvement of TNF-receptor activation. These findings suggest that the TNFα-induced hypersensitivity of vagal bronchopulmonary afferents may be responsible for, at least in part, the airway hyperresponsiveness caused by inhaled TNFα in healthy individuals.
登录
查看更多内容
DOI：
10.1165/ajrcmb.10.5.8179909
发表时间：
1994-05-01
影响因子：
6.4
作者：
BRADDING, P;ROBERTS, JA;HOLGATE, ST
通讯作者：
HOLGATE, ST
影响因子：
4.4
作者：
Barbin, G;Roisin, MP;Zalc, B
通讯作者：
Zalc, B
影响因子：
7.3
作者：
CUNHA, FQ;POOLE, S;FERREIRA, SH
通讯作者：
FERREIRA, SH
影响因子：
2.5
作者：
BALUK, P;NADEL, JA;MCDONALD, DM
通讯作者：
MCDONALD, DM
影响因子：
--
作者：
Gover, T D;Moreira, T H;Weinreich, D
通讯作者：
Weinreich, D