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Our goal was to show that PM<jats:sub>2.5<\/jats:sub> eliciting a proinflammatory response activates the immune\u2010pineal 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\u00a0hours reduced nocturnal plasma melatonin levels and increased lung melatonin levels. Melatonin synthesis in the lung reduced lipid peroxidation and increased PM<jats:sub>2.5<\/jats:sub> engulfment and cell viability by activating high\u2010affinity 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 NF\u03baB 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\u2010associated stimulus, which activates the immune\u2010pineal axis and provides a new framework for understanding the effects of air pollution on lung diseases.<\/jats:p>","DOI":"10.1111\/jpi.12636","type":"journal-article","created":{"date-parts":[[2020,2,11]],"date-time":"2020-02-11T12:56:50Z","timestamp":1581425810000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Immune\u2010pineal axis protects rat lungs exposed to polluted air"],"prefix":"10.1111","volume":"68","author":[{"given":"Claudia Emanuele","family":"Carvalho\u2010Sousa","sequence":"first","affiliation":[{"name":"Laboratory of Chronopharmacology Institute of Bioscience \u2013 University of S\u00e3o Paulo S\u00e3o Paulo 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