Effect of urban air pollution in São Paulo on pineal gland production of melatonin...
Immune-pineal axis: time-niology integrated to surveillance and defense
Multiuser equipment approved in grant 2013/13691-1 - for acquisition of AMNIS flow...
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Author(s): |
Cláudia Emanuele Carvalho de Sousa
Total Authors: 1
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Document type: | Doctoral Thesis |
Press: | São Paulo. |
Institution: | Universidade de São Paulo (USP). Instituto de Biociências (IBIOC/SB) |
Defense date: | 2015-05-15 |
Examining board members: |
Regina Pekelmann Markus;
Fernanda Gaspar do Amaral;
Cristoforo Scavone
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Advisor: | Regina Pekelmann Markus |
Abstract | |
Pathogen-associated molecular patterns (PAMPs) and pró-inflammatory cytokines activate the Immune-Pineal Axis promoting a temporary shift of melatonin synthesis from the pineal gland to immune-competent cells .This shift is mediated by the activation of the transcription factor nuclear factor kappa B (NF-κB ), which according to the cell milieu inhibits or induces the transcription of the gene that codifies the key enzyme in melatonin synthesis (arylalkylamine-N-acetyltransferase, AA-NAT), and alters melatonin function from chronobiotic to a regulator of inflammatory responses Our aim is to investigate whether air pollution, an important environmental danger-associated molecular pattern, triggers the immune-pineal axis. We investigated the effect of urban fine concentrated particulate matter (PM2.5, <2.5 mm) on the nocturnal melatonin synthesis in rats, and the effect of isolated derived diesel particles (DEP) on melatonin synthesis by RAW 264.7 cells, a model for studying macrophages. PM exposition increased nuclear translocation of NF-κB and reduced the pineal expression of AA-NAT and plasma melatonin concentration. In contrast, DEP leads to a transient translocation of NF-κB in RAW 274.6 cells resulting in the expression of AA-NAT and the synthesis of melatonin. We confirmed that the activation of κB elements in Aa-nat gene was responsible for its transcription. In conclusion, air pollution, which can be considered a danger-signalizing agent, activates the immune-pineal axis, reducing nocturnal pineal melatonin synthesis, and activating the production of melatonin by macrophages. (AU) |