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Immune-pineal axis protects rat lungs exposed to polluted air

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Autor(es):
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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]
Número total de Autores: 12
Afiliação do(s) autor(es):
[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
Número total de Afiliações: 4
Tipo de documento: Artigo Científico
Fonte: Journal of Pineal Research; v. 68, n. 3 FEB 2020.
Citações Web of Science: 0
Resumo

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)

Processo FAPESP: 13/13691-1 - Eixo imune-pineal: integrando a biologia do tempo em condições fisiológicas, fisiopatológicas e patológicas
Beneficiário:Regina Pekelmann Markus
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 12/04508-6 - O efeito da poluição urbana de São Paulo sobre a produção de melatonina pela glândula pineal e na reatividade das células endoteliais de rato.
Beneficiário:Eliana Paula Pereira
Linha de fomento: Bolsas no Brasil - Doutorado
Processo FAPESP: 11/50198-6 - Eixo imune-pineal: efeito da poluicao atmosferica.
Beneficiário:Regina Pekelmann Markus
Linha de fomento: Auxílio à Pesquisa - Regular