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Open AccessArticle

β-Adrenoceptors Trigger Melatonin Synthesis in Phagocytes

1
Laboratory of Chronopharmacology, Deartment of Physiology, Institute of Bioscience, University of São Paulo, 05508-900 São Paulo, Brazil
2
Laboratory of Neuroimmunoendocrinology, Department of Physiology, Institute of Bioscience, University of São Paulo, 05508-900 São Paulo, Brazil
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(8), 2182; https://doi.org/10.3390/ijms19082182
Received: 1 June 2018 / Revised: 12 July 2018 / Accepted: 16 July 2018 / Published: 26 July 2018
Melatonin (5-methoxy-N-acetylserotonin), the pineal hormone, is also synthesized by immune-competent cells. The pineal hormone signals darkness, while melatonin synthesized on demand by activated macrophages at any hour of the day acts locally, favoring regulatory/tolerant phenotypes. Activation of β-adrenoceptors in pinealocytes is the main route for triggering melatonin synthesis. However, despite the well-known role of β-adrenoceptors in the resolution macrophage phenotype (M2), and the relevance of macrophage synthesized melatonin in facilitating phagocytic activity, there is no information regarding whether activation of β-adrenoceptors would induce melatonin synthesis by monocytes. Here we show that catecholamines stimulate melatonin synthesis in bone marrow-derived dendritic cells and RAW 264.7 macrophages. Activation of β-adrenoceptors promotes the synthesis of melatonin by stimulating cyclic AMP/protein kinase A (PKA) pathway and by activating the nuclear translocation of NF-κB. Considering the great number of macrophages around sympathetic nerve terminals, and the relevance of this system for maintaining macrophages in stages compatible to low-grade inflammation, our data open the possibility that extra-pineal melatonin acts as an autocrine/paracrine signal in macrophages under resolution or tolerant phenotypes. View Full-Text
Keywords: melatonin; macrophages; beta-adrenergic receptors; immune-pineal axis; nuclear factor kappa B (NF-κB); extra-pineal melatonin synthesis melatonin; macrophages; beta-adrenergic receptors; immune-pineal axis; nuclear factor kappa B (NF-κB); extra-pineal melatonin synthesis
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MDPI and ACS Style

Pires-Lapa, M.A.; Carvalho-Sousa, C.E.; Cecon, E.; Fernandes, P.A.; Markus, R.P. β-Adrenoceptors Trigger Melatonin Synthesis in Phagocytes. Int. J. Mol. Sci. 2018, 19, 2182.

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