Environmental pollution in the form of particulate matter <2.5 μm (PM2.5 ) is a major risk factor for diseases such as lung cancer, chronic respiratory infections, and major cardiovascular diseases. Our goal was to show that PM2.5 eliciting a proinflammatory response activates the immune-pineal axis, reducing the pineal synthesis and increasing the extrapineal synthesis of melatonin. Herein, we report that the exposure of rats to polluted air for 6 hours reduced nocturnal plasma melatonin levels and increased lung melatonin levels. Melatonin synthesis in the lung reduced lipid peroxidation and increased PM2.5 engulfment and cell viability by activating high-affinity melatonin receptors. Diesel exhaust particles (DEPs) promoted the synthesis of melatonin in a cultured cell line (RAW 264.7 cells) and rat alveolar macrophages via the expression of the gene encoding for AANAT through a mechanism dependent on activation of the NFκB pathway. Expression of the genes encoding AANAT, MT1, and MT2 was negatively correlated with cellular necroptosis, as disclosed by analysis of Gene Expression Omnibus (GEO) microarray data from the human alveolar macrophages of nonsmoking subjects. The enrichment score for antioxidant genes obtained from lung gene expression data (GTEx) was significantly correlated with the levels of AANAT and MT1 but not the MT2 melatonin receptor. Collectively, these data provide a systemic and mechanistic rationale for coordination of the pineal and extrapineal synthesis of melatonin by a standard damage-associated stimulus, which activates the immune-pineal axis and provides a new framework for understanding the effects of air pollution on lung diseases.

中文翻译：

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免疫松轴保护暴露于污染空气中的大鼠肺。

颗粒物<2.5μm（PM2.5）形式的环境污染是导致肺癌，慢性呼吸道感染和重大心血管疾病等疾病的主要危险因素。我们的目标是证明引起促炎性反应的PM2.5激活了免疫松树轴，减少了松果体的合成并增加了褪黑激素的松果外合成。本文中，我们报道大鼠暴露于污染空气中6小时可降低夜间血浆褪黑激素水平，并增加肺褪黑激素水平。通过激活高亲和力的褪黑激素受体，肺中的褪黑素合成可减少脂质过氧化作用并增加PM2.5吞噬和细胞活力。柴油机废气颗粒（DEP）促进了培养的细胞系中的褪黑激素合成（RAW 264。7细胞）和大鼠肺泡巨噬细胞通过依赖于NFκB途径激活的机制表达编码AANAT的基因。编码AANAT，MT1和MT2的基因的表达与细胞坏死呈负相关，这是通过对来自非吸烟对象的人肺泡巨噬细胞的基因表达综合（GEO）微阵列数据的分析所揭示的。从肺基因表达数据（GTEx）获得的抗氧化剂基因的富集得分与AANAT和MT1的水平显着相关，而与MT2褪黑激素受体却没有显着相关。总体而言，这些数据为通过标准伤害相关刺激来协调松果体和松果体褪黑激素合成提供了系统和机械的理论依据，