Immune-pineal axis protects rat lungs exposed to polluted air

Author(s):Show less -

Carvalho-Sousa, Claudia Emanuele ^[1] ; Pereira, Eliana P. ^[1] ; Kinker, Gabriela S. ^[1] ; Veras, Mariana ^[2] ; Ferreira, Zulma S. ^{[1, 3]} ; Barbosa-Nunes, Fernanda P. ^[3] ; Martins, Joilson O. ; Saldiva, Paulo H. N. ^[2] ; Reiter, Russel J. ^[4] ; Fernandes, Pedro A. ^[1] ; da Silveira Cruz-Machado, Sanseray ^[1] ; Markus, Regina P. ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Biosci, Lab Chronopharmacol, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Fac Med, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Fac Pharm & Biochem, Sao Paulo - Brazil

^[4] Univ Texas Hlth Ctr San Antonio, Fac Med, San Antonio, TX - USA

• Document type: Journal article
• Source: Journal of Pineal Research; v. 68, n. 3 FEB 2020.
• Web of Science Citations: 0

Abstract

Environmental pollution in the form of particulate matter <2.5 mu m (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 NF kappa B 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. (AU)

• FAPESP's process: 13/13691-1 - Immune-pineal axis: time-niology integrated to surveillance and defense
• Grantee: Regina Pekelmann Markus
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 12/04508-6 - Effect of urban air pollution in São Paulo on pineal gland production of melatonin and on the rat endothelial cell reactivity.
• Grantee: Eliana Paula Pereira
• Support Opportunities: Scholarships in Brazil - Doctorate