Department of Internal Medicine, Pulmonary, Critical Care & Sleep division, University of Nebraska Medical Center, Omaha, NE, 68198, USA.
Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, CO, USA.
Sci Rep. 2023 Feb 16;13(1):2767. doi: 10.1038/s41598-023-29781-9.
Dietary long-chain omega-3 polyunsaturated fatty acids (n-3 PUFA) and their pro-resolving metabolites are protective against atherosclerotic disease, and ameliorate systemic inflammatory conditions including lupus erythematosus, psoriasis, and bronchial asthma. Organic bioaerosol inhalation is a common and injurious hazard associated with agricultural occupations such as work in swine concentrated animal feeding operations (CAFOs) and is known to increase the risk for developing respiratory conditions such as asthma and COPD. Nearly all cells secrete membrane-bound vesicles (extracellular vesicles, EVs) that have the capacity to transmit protein, nucleic acid, and lipid signaling mediators between cells. Using a polymer-based isolation technique (ExoQuick, PEG) followed by ultracentrifugation, EVs were isolated from CAFO dust extracts, and were quantified and partially characterized. Here, we investigated the role of the n-3 PUFA docosahexaenoic acid (DHA) as a component of n-6 to n-3 PUFA mixtures used to recapitulate physiologically relevant dietary ratios in the resolution of inflammatory injury caused by exposure to EVs carried by agricultural organic dust in vitro. Primary human bronchial epithelial cells, fibroblasts and monocyte-derived macrophages were exposed to EVs isolated from swine CAFO dust. Cells were treated with mixtures of n-6 and n-3 PUFA during recovery from the EV-induced injury. CAFO dust extract (DE) was found to contain EVs that contributed significantly to the overall consequences of exposure to complete DE. DHA-rich PUFA ratios inhibited DE-derived EV-induced proinflammatory cytokine release dose-dependently. DHA-rich PUFA ratios also reversed the damaging effects of EVs on recellularization of lung matrix scaffolds, accelerated wound healing, and stimulated the release of pro-resolution mediators. These results underscore the importance of n-3 PUFA as anti-inflammatory compounds during recovery from EV-laden environmental dust exposure in the context of cellular responses in vitro, warranting future translational studies.
饮食中长链 ω-3 多不饱和脂肪酸（n-3PUFA）及其促解决代谢产物可预防动脉粥样硬化疾病，并改善包括红斑狼疮、银屑病和支气管哮喘在内的全身性炎症状态。有机生物气溶胶吸入是与农业职业相关的常见且有害的危害，例如在集约化养猪场（CAFO）工作时，已知它会增加患哮喘和 COPD 等呼吸道疾病的风险。几乎所有细胞都会分泌膜结合囊泡（细胞外囊泡，EVs），这些囊泡能够在细胞之间传递蛋白质、核酸和脂质信号介质。我们使用基于聚合物的分离技术（ExoQuick，PEG）和超速离心法从 CAFO 粉尘提取物中分离 EVs，并对其进行定量和部分表征。在这里，我们研究了 n-3PUFA 二十二碳六烯酸（DHA）作为 n-6 到 n-3PUFA 混合物的一部分的作用，该混合物用于模拟生理相关饮食比例，以解决体外暴露于农业有机粉尘携带的 EV 引起的炎症损伤。原代人支气管上皮细胞、成纤维细胞和单核细胞衍生的巨噬细胞暴露于从猪 CAFO 粉尘中分离的 EV。细胞在用 EV 诱导损伤恢复期间用 n-6 和 n-3PUFA 混合物处理。CAFO 粉尘提取物（DE）被发现含有对暴露于完整 DE 的总体后果有重大贡献的 EV。富含 DHA 的 PUFA 比例可抑制 DE 衍生的 EV 诱导的促炎细胞因子释放，呈剂量依赖性。富含 DHA 的 PUFA 比例还逆转了 EV 对肺基质支架再细胞化的破坏性影响，加速了伤口愈合，并刺激了促解决介质的释放。这些结果强调了 n-3PUFA 在 EV 负载环境粉尘暴露后细胞恢复过程中作为抗炎化合物的重要性，这在体外细胞反应背景下需要进行未来的转化研究。
