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1.
Int J Mol Sci ; 19(8)2018 Jul 26.
Article in English | MEDLINE | ID: mdl-30049944

ABSTRACT

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 ß-adrenoceptors in pinealocytes is the main route for triggering melatonin synthesis. However, despite the well-known role of ß-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 ß-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 ß-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.


Subject(s)
Macrophages/metabolism , Melatonin/metabolism , Phagocytes/metabolism , Receptors, Adrenergic, beta/metabolism , Animals , Biosynthetic Pathways , Cells, Cultured , Cyclic AMP-Dependent Protein Kinases/metabolism , Male , Mice , Mice, Inbred BALB C , RAW 264.7 Cells , Signal Transduction
2.
J Pineal Res ; 55(3): 240-6, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23745599

ABSTRACT

Many cells in the organism besides pinealocytes, synthesize melatonin. Here, we evaluate both the mechanism of zymosan-induced melatonin synthesis and its autocrine effect in human colostral mononuclear cells. The synthesis of melatonin was induced by activation of the transcription factor nuclear factor kappa B (NF-κB), as either the blockade of the proteasome or the binding of NF-κB to DNA inhibits zymosan-induced melatonin synthesis. As observed in RAW 264.7 lineage cells, the dimer involved is RelA/c-Rel. Melatonin plays a direct role in mononuclear cell activity, increasing zymosan-induced phagocytosis by stimulating MT2 melatonin receptors and increasing the expression of dectin-1. This role was confirmed by the blockade of melatonin receptors using the competitive antagonist luzindole and the MT2 -selective partial agonist 4P-PDOT. In summary, we show that melatonin produced by immune-competent cells acts in an autocrine manner, enhancing the clearance of pathogens by increasing phagocyte efficiency. Given that these cells are present in human colostrum for 4 or 5 days after birth, this mechanism may be relevant for the protection of infant health.


Subject(s)
Colostrum/metabolism , Lectins, C-Type/metabolism , Leukocytes, Mononuclear/metabolism , Melatonin/biosynthesis , Phagocytosis/physiology , Adolescent , Adult , Animals , Cell Line , Colostrum/cytology , DNA-Binding Proteins/metabolism , Female , Humans , Infant, Newborn , Leukocytes, Mononuclear/cytology , Melatonin/antagonists & inhibitors , Mice , Nuclear Proteins/metabolism , Phagocytosis/drug effects , Proto-Oncogene Proteins c-rel , Tetrahydronaphthalenes/pharmacology , Transcription Factor RelA/metabolism , Tryptamines/pharmacology
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