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Effect of atmospheric pollution of São Paulo on the Imune-Pineal Axis

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Author(s):
Cláudia Emanuele Carvalho de Sousa
Total Authors: 1
Document type: Doctoral Thesis
Press: São Paulo.
Institution: Universidade de São Paulo (USP). Instituto de Biociências (IBIOC/SB)
Defense date:
Examining board members:
Regina Pekelmann Markus; Fernanda Gaspar do Amaral; Cristoforo Scavone
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-&kappa;B ), 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-&kappa;B and reduced the pineal expression of AA-NAT and plasma melatonin concentration. In contrast, DEP leads to a transient translocation of NF-&kappa;B in RAW 274.6 cells resulting in the expression of AA-NAT and the synthesis of melatonin. We confirmed that the activation of &kappa;B 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)