Agricultural workers, especially those who work in swine confinement facilities, are at increased risk for developing pulmonary diseases including asthma, chronic obstructive pulmonary disease, and chronic bronchitis due to exposures to fumes, vapors, and organic dust. Repetitive exposure to agricultural dust leads to unresolved inflammation, a common underlying mechanism that worsens lung disease. Besides occupational exposure to dusts, diet also significantly contributes to inflammation and disease progression. Since DHA (docosahexaenoic acid), a polyunsaturated omega-3 fatty acid and its bioactive metabolites have key roles in inflammation resolution, we rationalized that individuals chronically exposed to organic dusts can benefit from dietary modifications. Here, we evaluated the role of DHA in modifying airway inflammation in a murine model of repetitive exposure to an aqueous extract of agricultural dust (three-week exposure to swine confinement dust extract, HDE) and after a one-week resolution/recovery period. We found that mice fed a high DHA diet had significantly increased bronchoalveolar lavage fluid (BALF) levels of DHA-derived resolvins and lower TNFα along with altered plasma levels of endocannabinoids and related lipid mediators. Following the one-week recovery we identified significantly reduced BALF cellularity and cytokine/chemokine release along with increased BALF amphiregulin and resolvins in DHA diet-fed versus control diet-fed mice challenged with HDE. We further report observations on the effects of repetitive HDE exposure on lung Ym1+ and Arg-1+ macrophages. Overall, our findings support a protective role for DHA and identify DHA-derived resolvins and endocannabinoids among the potential mediators of DHA in altering airway inflammation in chronic agricultural dust exposure.

农业工人，特别是在养猪场工作的工人，由于接触烟雾、蒸汽和有机粉尘，患肺部疾病的风险增加，包括哮喘、慢性阻塞性肺病和慢性支气管炎。反复接触农业粉尘会导致未解决的炎症，这是导致肺部疾病恶化的常见潜在机制。除了职业性接触粉尘外，饮食也会显着促进炎症和疾病进展。由于 DHA（二十二碳六烯酸）是一种多不饱和 omega-3 脂肪酸及其生物活性代谢物在炎症消退中发挥着关键作用，因此我们认为长期接触有机粉尘的个体可以从饮食调整中受益。在这里，我们在重复暴露于农业粉尘水提取物（暴露于猪圈养粉尘提取物，HDE）三周以及经过一周的缓解/恢复期后的小鼠模型中评估了 DHA 在改变气道炎症方面的作用。我们发现，喂食高 DHA 饮食的小鼠，支气管肺泡灌洗液 (BALF) 中 DHA 衍生溶解素的水平显着升高，TNFα 降低，同时内源性大麻素和相关脂质介质的血浆水平发生改变。恢复一周后，我们发现，与接受 HDE 攻击的对照饮食喂养小鼠相比，DHA 饮食喂养的小鼠 BALF 细胞结构和细胞因子/趋化因子释放显着减少，同时 BALF 双调蛋白和消退素增加。我们进一步报告了重复暴露 HDE 对肺 Ym1+ 和 Arg-1+ 巨噬细胞影响的观察结果。 总体而言，我们的研究结果支持 DHA 的保护作用，并确定 DHA 衍生的分解素和内源性大麻素是 DHA 改变慢性农业粉尘暴露中气道炎症的潜在介质。