Immune-pineal axis protects rat lungs exposed to polluted air

Claudia Emanuele Carvalho-Sousa, Eliana P. Pereira, Gabriela S. Kinker, Mariana Veras, Zulma S. Ferreira, Fernanda P. Barbosa-Nunes, Joilson O. Martins, Paulo H.N. Saldiva, Russel J. Reiter, Pedro A. Fernandes, Sanseray da Silveira Cruz-Machado, Regina P. Markus

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


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.

Original languageEnglish (US)
Article numbere12636
JournalJournal of pineal research
Issue number3
StatePublished - Apr 1 2020


  • NF-kappa B
  • alveolar macrophages
  • diesel particle
  • immune-pineal axis
  • phagocytosis

ASJC Scopus subject areas

  • Endocrinology


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