Effects of naphthoquinone on airway responsiveness in the presence or absence of antigen in mice
Effects of naphthoquinone on airway responsiveness in the presence or absence of antigen in mice
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DOI：
10.1007/s00204-007-0186-5
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发表时间：
2007-08-01
影响因子：
6.1
通讯作者：
Kumagai, Yoshito
中科院分区：
文献类型：
--
作者：
Inoue, Ken-ichiro;Takano, Hirohisa;Kumagai, Yoshito
我们最近已经证明，萘醌（NQ）（柴油机排气颗粒（DEP）的可提取化合物之一）增强小鼠中抗原相关的气道炎症伴杯状细胞增生（Inoue等人，Eur Respir J 209（2）：259-267，2007）。此外，NQ增强了白细胞介素（IL）-4和IL-5的肺表达。然而，NQ对哮喘其他主要特征的影响尚未完全研究。本研究的目的是评估NQ对模型气道反应性的影响。将媒介物、NQ、卵清蛋白（OVA）或NQ + OVA经肠道内施用至ICR小鼠，持续6周。末次滴注后24 h，检测肺组织学、肺功能（如总呼吸系统阻力（R）和牛顿阻力（R-n））以及肺中IL- 13蛋白水平和MUC 5AC mRNA水平。反复暴露于NQ加重了抗原相关的肺部炎症。与媒介物相比，单独的NQ增强了R和R-n，但无统计学显著性。单独的OVA或NQ加OVA显示R和R-n的增加，这在NQ加OVA中是显著的（相对于媒介物P < 0.05）。与单独暴露于NQ或OVA相比，联合暴露于NQ和OVA会升高肺部IL-13和MUC 5AC的水平。这些结果表明，NQ可以在存在或不存在抗原的情况下增强气道高反应性。此外，肺组织中IL-13和MUC 5AC的表达增加可能部分地导致了NQ对哮喘特征的恶化。
We have recently demonstrated that naphthoquinone (NQ), one of extractable chemical compounds of diesel exhaust particles (DEP), enhances antigen-related airway inflammation with goblet cell hyperplasia in mice (Inoue et al. in Eur Respir J 209(2):259-267, 2007). Further, NQ has enhanced lung expressions of interleukin (IL)-4 and IL-5. However, the effects of NQ on other cardinal features of asthma have not been completely investigated. The aim of the present study was to evaluate the effects of NQ on airway responsiveness on the model. Vehicle, NQ, ovalbumin (OVA), or NQ + OVA was administered intratarcheally to ICR mice for 6 weeks. Twenty-four hours after the last instillation, lung histology, lung functions such as total respiratory system resistance (R) and Newtonian resistance (R-n), and protein level of IL- 13 and mRNA level for MUC5AC in the lung were examined. Repetitive exposure to NQ aggravated antigen-related lung inflammation. NQ alone enhanced R and R-n as compared to vehicle without statistical significance. OVA alone or NQ plus OVA showed increases in R and R-n, which was prominent in NQ plus OVA (P < 0.05 vs. vehicle). Combined exposure to NQ and OVA elevated the levels of IL-13 and MUC5AC in the lung as compared with exposure to NQ or OVA alone. These results indicate that NQ can enhance airway hyperresponsiveness in the presence or absence of an antigen. Also, amplified lung expressions of IL-13 and MUC5AC might partly contribute to the deterioration of asthma features by NQ.