Aspirin-Triggered Resolvin D1 Reduces Chronic Dust-Induced Lung Pathology without Altering Susceptibility to Dust-Enhanced Carcinogenesis.
Aspirin-Triggered Resolvin D1 Reduces Chronic Dust-Induced Lung Pathology without Altering Susceptibility to Dust-Enhanced Carcinogenesis.
复制标题
阿司匹林触发的Resolvin D1减少慢性粉尘诱导的肺部病理学，而不改变对粉尘增强致癌作用的易感性。
作者：
农场工人因每天接触有机粉尘而患急性和慢性肺炎性疾病的风险增加。以前的研究已经检查了小鼠单次和重复暴露于猪禁闭设施的灰尘的炎症效应，但是，没有研究在慢性模型中探索这些效应。为了解决这一研究空白，我们建立了肺肿瘤发生的慢性粉尘暴露小鼠模型，该模型也用于测量omega-3脂肪酸衍生的脂质介质作为减轻这些诱导反应的治疗剂的功效。我们从这些调查的结果是第一次评估慢性炎症，这些粉尘的致癌作用，以及确定一个潜在的治疗策略，通过使用ω-3脂肪酸衍生的生物活性脂质介质减轻炎症的影响。肺癌是全球癌症相关死亡的主要原因，与未解决或慢性炎症相关的风险增加。农业和畜牧业工人忍受大量暴露于农业粉尘的日常基础上，然而，这些粉尘暴露的慢性炎症和致癌作用尚不清楚。我们已经开发了一种慢性粉尘暴露模型的肺癌发生，其中小鼠鼻内挑战每周三次，持续24周，使用水溶性粉尘提取物（HDE）从收集在猪禁闭设施的粉尘。我们还用omega-3-脂肪酸脂质介质阿司匹林触发的消退素D1（AT-RvD 1）治疗小鼠，以提供一种减轻HDE炎症和致癌作用的新治疗策略。相对于盐水暴露小鼠，暴露于HDE导致显著的免疫细胞流入肺部，增强肺肿瘤发生，严重的组织发病机制以及促炎和致癌基因特征。AT-RvD 1治疗减轻了灰尘诱导的炎症反应，但不能防止HDE + NNK增强的肿瘤发生。我们的数据表明，慢性HDE暴露诱导显著的炎症和促癌反应，而AT-RvD 1治疗抑制炎症反应，为AT-RvD 1缓解慢性炎症的治疗用途提供了强有力的论据。
Farm workers are at an increased risk of developing acute and chronic lung inflammatory diseases from their everyday exposure to organic dust. Previous investigations have examined the inflammatory effects in mice from single and repetitive exposure to dust from swine confinement facilities, however, no study has explored these effects in a chronic model. To address this research gap, we established a chronic dust exposure mouse model of lung tumorigenesis that was also used to measure the efficacy of omega-3 fatty acid-derived lipid mediators as therapeutics for mitigating these induced responses. Our results from these investigations are the first to evaluate the chronic inflammatory, and carcinogenic effects of these dusts, as well as identify a potential therapeutic strategy for mitigating the inflammatory effects by using an omega-3 fatty acid-derived bioactive lipid mediator. Lung cancer is the leading cause of cancer-related deaths worldwide, with increased risk being associated with unresolved or chronic inflammation. Agricultural and livestock workers endure significant exposure to agricultural dusts on a routine basis; however, the chronic inflammatory and carcinogenic effects of these dust exposure is unclear. We have developed a chronic dust exposure model of lung carcinogenesis in which mice were intranasally challenged three times a week for 24 weeks, using an aqueous dust extract (HDE) made from dust collected in swine confinement facilities. We also treated mice with the omega-3-fatty acid lipid mediator, aspirin-triggered resolvin D1 (AT-RvD1) to provide a novel therapeutic strategy for mitigating the inflammatory and carcinogenic effects of HDE. Exposure to HDE resulted in significant immune cell influx into the lungs, enhanced lung tumorigenesis, severe tissue pathogenesis, and a pro-inflammatory and carcinogenic gene signature, relative to saline-exposed mice. AT-RvD1 treatment mitigated the dust-induced inflammatory response but did not protect against HDE + NNK-enhanced tumorigenesis. Our data suggest that chronic HDE exposure induces a significant inflammatory and pro-carcinogenic response, whereas treatment with AT-RvD1 dampens the inflammatory responses, providing a strong argument for the therapeutic use of AT-RvD1 to mitigate chronic inflammation.
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影响因子：
3.7
作者：
Hsiao HM;Sapinoro RE;Thatcher TH;Croasdell A;Levy EP;Fulton RA;Olsen KC;Pollock SJ;Serhan CN;Phipps RP;Sime PJ
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12.3
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