Melatonin antagonizes ozone-exacerbated asthma by inhibiting the TRPV1 channel and stabilizing the Nrf2 pathway

褪黑素 支气管肺泡灌洗 谷胱甘肽 免疫印迹 化学 氧化应激 免疫球蛋白E 内分泌学 内科学 免疫学 医学 抗体 生物化学 基因
作者
Yushan Chen,Xiaoyu Wu,Yang Xu,Xudong Liu,Yan Zeng,Jinquan Li
出处
期刊:Environmental Science and Pollution Research [Springer Nature]
卷期号:28 (42): 59858-59867 被引量:14
标识
DOI:10.1007/s11356-021-14945-9
摘要

Over the past few years, ozone has been identified as a potential risk factor for exacerbating asthma. However, few attempts have been made to prevent the progression of ozone-exacerbated asthma. This study investigated the attenuating effects of melatonin on ozone-aggravated allergic asthma, and explored the changes to the transient receptor potential vanilloid 1 (TRPV1)-nuclear factor erythroid-derived 2-related factor 2 (Nrf2) pathway associated with melatonin treatment. The levels of TRPV1 and calcitonin gene-related peptides (CGRP) in lung tissue were detected by immunohistochemistry, western blot, and enzyme-linked immunosorbent assay (ELISA). The Nrf2 signaling involved proteins and mRNA were evaluated by western blot and RT-qPCR. The change of Immunoglobulin E (IgE) and T helper (Th) 2 and Th17 cytokines in serum and bronchoalveolar lavage fluid (BALF) was determined by ELISA. Recruitment of inflammatory cells in BALF, histopathological changes, and airway hyperresponsiveness (AHR) were also determined in lung tissues. Our results indicated that melatonin treatment significantly reduced oxidative stress, as indicated by levels of glutathione (GSH), malonaldehyde (MDA), and 8-hydroxy-2-deoxyguanosine (8-OH-dG). Moreover, ozone-exacerbated asthma symptoms, such as inflammatory cell infiltration, levels of serum immunoglobulin, Th2 and Th17 cytokines in BALF, obvious changes in lung histology, and AHR, were all ameliorated by melatonin treatment. Interestingly, melatonin not only markedly decreased the protein levels of TRPV1 and CGRP, but also enhanced the expression of Nrf2, quinone oxidoreductase-1 (NQO-1), and heme oxygenase-1 (HO-1). Taken together, our results demonstrate that melatonin administration could antagonize ozone-exacerbated asthma by inhibiting the TRPV1 channel and stabilizing the Nrf2 pathway.
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