PM2.5 induces airway hyperresponsiveness and inflammation via the AhR pathway in a sensitized Guinea pig asthma-like model
PM2.5 induces airway hyperresponsiveness and inflammation via the AhR pathway in a sensitized Guinea pig asthma-like model
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DOI：
10.1016/j.tox.2021.153026
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发表时间：
2021-11-16
期刊：
影响因子：
4.5
通讯作者：
De Vizcaya-Ruiz, Andrea
中科院分区：
文献类型：
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作者：
Morales-Rubio, Russell;Amador-Munoz, Omar;De Vizcaya-Ruiz, Andrea
暴露于细颗粒物（PM2.5）会诱发气道炎症和高反应性，从而导致哮喘。有关机制仍在调查中。我们研究了白藜芦醇（3，4 '，5-三羟基二苯乙烯）（RES）对过敏性哮喘实验豚鼠模型中PM2.5暴露诱导的气道高反应性、炎症和CYP 1A 1蛋白表达（芳烃受体（AhR）靶点）的影响。多酚化合物RES由于其抗氧化和抗炎特性而被用作AhR的拮抗剂;因此，提供了机理见解。动物用氢氧化铝和卵清蛋白致敏，并暴露于过滤空气或PM2.5。使用全身室颗粒浓缩器（5小时/天）暴露于PM2.5 15天。动物接受生理盐水或RES（10 mg/kg/天）口服21天，同时进行OVA激发或PM2.5暴露。（暴露室中平均433 +/- 111 μ g/m3）在OVA激发的动物中诱导了哮喘样表型，其特征是对乙酰胆碱（ACh）使用flexiVent系统（R）进行评价。支气管肺泡灌洗液（BALF）中的促炎细胞因子（IL-6、IL-17、TNF-α和IFN-γ）、炎性细胞（嗜酸性粒细胞和中性粒细胞）和肺CYP 1A 1也平行增加。RES显着抑制气道高反应性，炎症，和CYP 1A 1蛋白表达在OVA激发的PM2.5 exposedanimals.In总结，使用RES，我们证明，PM诱导的气道高反应性是由炎症反应通过AhR途径在过敏性哮喘豚鼠模型。
Exposure to fine particulate matter (PM2.5) induces airway inflammation and hyperreactivity that lead to asthma. The mechanisms involved are still under investigation. We investigated the effect of resveratrol (3,4',5-trihydroxystilbene) (RES) on airway hyperresponsiveness, inflammation and CYP1A1 protein expression (an aryl hydrocarbon receptor (AhR) target) induced by PM2.5 exposure in an allergic asthma experimental guinea pig model. The polyphenolic compound RES was used due to its antioxidant and anti-inflammatory properties and as an antagonist of the AhR; thus, providing mechanistic insights.Animals were sensitized with aluminum hydroxide and ovalbumin and exposed to filtered air or PM2.5. Exposure to PM2.5 was conducted using a whole-body chamber particle concentrator (5 h/day) for 15 days. Animals received saline solution or RES (10 mg/kg per day) orally for 21 days simultaneously to the OVA challenge or PM2.5 exposure.PM2.5 exposure (mean 433 +/- 111 mu g/m(3) in the exposure chamber) in OVA challenged animals induced an asthma-like phenotype characterized by increased baseline lung resistance (Rrs) and central airway resistance (Rn) in response to acetylcholine (ACh) evaluated using a flexiVent system (R). A parallel increase of proinflammatory cytokines (IL-6, IL-17, TNF-alpha and IFN-gamma), inflammatory cells (eosinophils and neutrophils) in bronchoalveolar lavage fluid (BALF) and lung CYP1A1 increase also occurred. RES significantly inhibited airway hyperresponsiveness, inflammation, and CYP1A1 protein expression in the OVA-challenged PM2.5 exposed animals.In summary, with the use of RES we demonstrate that PM-induced airway hyperreactivity is modulated by the inflammatory response via the AhR pathway in an allergic asthma guinea pig model.