Ozone (O₃) is an air pollutant that induces pulmonary inflammation and injury, leading to increased susceptibility and exacerbation of chronic lung diseases. Furthermore, ambient O₃ levels are expected to rise with increasing global temperatures. Docosahexaenoic acid (DHA) is an omega-3 (n-3) polyunsaturated fatty acid (PUFA) primarily found in oily fish that reduces inflammation and enhances the resolution of inflammation. This is partially attributed to DHA-derived oxylipins termed specialized pro-resolving mediators (SPMs) that have anti-inflammatory/pro-resolving properties. However, whether dietary DHA protects the lungs from O3-induced inflammation and injury is unclear. We hypothesized that dietary DHA supplementation increases pulmonary SPMs and thereby decreases O₃-induced pulmonary inflammation. To test this, C57BL/6J mice were fed control diet or DHA-enriched diet (2% kcal from DHA) for 6 weeks, exposed to filtered air (FA) or 1 ppm O₃ for 3h (comparable to an O₃ Action Day for humans), and necropsied 24h or 48h following exposure. DHA supplementation reduced airspace neutrophilia, decreased cytokine production, and promoted transcriptomic signatures for leukocyte chemotaxis and fatty acid oxidation. Furthermore, dietary DHA increased pulmonary DHA and its oxylipins while decreasing pro-inflammatory n-6 PUFAs and their oxylipins. Oropharyngeal aspiration of DHA-oxylipins 14-HDHA or maresin 1 (MaR1) decreased O₃-induced airspace neutrophilia and reduced bone marrow-derived macrophage production of neutrophil chemokines Cxcl1 and Cxcl2. These findings reveal that dietary DHA protects the lungs from O₃ exposure by driving 14-HDHA and MaR1 production, which reduces neutrophil recruiting chemokine production by macrophages. This pathway highlights a potential therapeutic dietary approach for mitigating air pollution-induced pulmonary inflammation.

Keywords: inflammation; lung; ozone; polyunsaturated fatty acids.

臭氧（O₃）是一种空气污染物，可诱发肺部炎症和损伤，从而增加慢性肺疾病的发生率和恶化。此外，随着全球气温的升高，环境中的臭氧水平预计会进一步上升。二十二碳六烯酸（DHA）是一种主要存在于油性鱼类中的ω-3多不饱和脂肪酸（PUFA），能够减少炎症并促进炎症的消退。这在一定程度上归因于一种称为特异性促解决介质（SPMs）的衍生自DHA的氧化脂质，它们具有抗炎/促解决特性。然而，膳食中补充DHA是否能保护肺部免受臭氧引起的炎症和损伤尚不清楚。我们假设，通过膳食补充DHA可以增加肺部中的SPMs水平，从而减少臭氧诱导的肺部炎症。为了验证这一假设，C57BL/6J小鼠在六周内被喂食对照饮食或富含DHA（2%能量来自DHA）的饮食，并暴露于过滤空气（FA）或1 ppm的臭氧（持续3小时，相当于人类的臭氧行动日），然后分别在暴露后24小时和48小时进行解剖。补充DHA减少了肺泡内中性粒细胞的数量，降低了细胞因子的产生，并促进了促进白细胞趋化作用和脂肪酸氧化的转录组特征。此外，膳食中的DHA增加了肺部的DHA及其氧化脂质水平，同时减少了促炎性的n-6 PUFA及其氧化脂质的水平。通过口服给予DHA氧化脂质14-HDHA或马雷辛1（MaR1），可以减少臭氧诱导的肺泡中性粒细胞数量，并降低骨髓衍生巨噬细胞产生中性粒细胞趋化因子Cxcl1和Cxcl2的水平。这些发现揭示了通过促进14-HDHA和MaR1的生成，膳食中的DHA能够保护肺部免受臭氧暴露的影响，进而减少巨噬细胞产生的中性粒细胞趋化因子的产生。这一途径强调了一种潜在的饮食治疗方法，用于减轻空气污染引起的肺部炎症。

关键词：炎症；肺部；臭氧；多不饱和脂肪酸。