Linalool attenuates lung inflammation induced by Pasteurella multocida via activating Nrf-2 signaling pathway
Linalool attenuates lung inflammation induced by Pasteurella multocida via activating Nrf-2 signaling pathway
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芳樟醇通过激活 Nrf-2 信号通路减轻多杀性巴氏杆菌诱导的肺部炎症
DOI：
10.1016/j.intimp.2014.05.030
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发表时间：
2014
影响因子：
5.6
通讯作者：
Feng Haihua
中科院分区：
文献类型：
--
作者：
Wu Qianchao;Yu Lijun;Qiu Jiaming;Shen Bingyu;Wang Di;Soromou Lanan Wassy;Feng Haihua
由多杀性巴氏杆菌引起的巴氏杆菌病常表现为养殖小反刍动物的呼吸道感染。虽然P.多杀性疾病主要以肺炎的形式出现，但关于在宿主-病原体相互作用的环境中在疾病发病机制中发挥作用的宿主因素的信息有限。核因子-红细胞2相关因子2（nuclear factor-erythroid 2 related factor 2，Nrf-2）是一种重要的炎症和免疫调节因子，通过控制氧化应激，在P诱导的炎症过程中发挥重要作用。多杀性在这项研究中，芳樟醇，在几个芳香植物物种的精油的天然化合物，提高核Nrf-2蛋白易位在A549肺细胞系和体内。P。Nrf-2 siRNA消除了多杀性诱导的促炎细胞因子表达。芳樟醇延迟治疗可减少肺中性粒细胞聚集，增强P。多杀性此外，芳樟醇显著增加了由Nrf-2调节的抗氧化酶的表达，并降低了肺组织中几种促炎细胞因子的水平，包括肿瘤坏死因子α（TNF-α）和白细胞介素（IL）-6。此外，用芳樟醇处理的动物在存活率方面有显著改善。这些发现揭示了芳樟醇作为一种新的Nrf-2激活剂，用于病原体介导的肺部炎症的新治疗策略。
Pasteurellosis caused by Pasteurella multocida manifest often as respiratory infection in farmed small ruminants. Although the incidence of pasteurellosis due toP. multocidamainly takes the form of pneumonia, there is limited information on host factors that play a role in disease pathogenesis in the milieu of host–pathogen interactions. Nuclear factor-erythroid 2 related factor 2 (Nrf-2), a critical regulator for various inflammatory and immune responses by controlling oxidative stress, may play an important role in the processes of inflammation induced byP. multocida. In this study, linalool, a natural compound of the essential oils in several aromatic plant species, elevated nuclear Nrf-2 protein translocation in the A549 lung cell line and in vivo. TheP. multocida-induced pro-inflammatory cytokines expression was abrogated by Nrf-2 siRNA. Postponed treatment with linalool decreased lung neutrophil accumulation and enhanced clearance ofP. multocida. Furthermore, linalool significantly increased the expression of antioxidant enzymes regulated by Nrf-2 and diminished lung tissue levels of several pro-inflammatory cytokines, including tumor necrosis factor α (TNF-α) and interleukin (IL)-6. In addition, animals treated with linalool had a marked improvement in survival. These findings have uncovered that linalool acts as a novel Nrf-2 activator for a novel therapeutic strategy in pathogen-mediated lung inflammation.