title: Melatonin synthesis in human colostrum mononuclear cells enhances dectin-1-mediated phagocytosis by mononuclear cells.
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.
authors.affiliation: Laboratory of Chronopharmacology, Institute of Bioscience, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Marco A
authors.initials: MA
authors.lastname: Pires-Lapa
authors.forename: Eduardo K
authors.initials: EK
authors.lastname: Tamura
authors.forename: Eugenia M A
authors.initials: EM
authors.lastname: Salustiano
authors.forename: Regina P
authors.initials: RP
authors.lastname: Markus
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D002460:Cell Line; D003126:Colostrum / Q000166:cytology / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D037181:Lectins, C-Type / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism*; D008550:Melatonin / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects / Q000502:physiology*; D020569:Proto-Oncogene Proteins c-rel; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D051996:Transcription Factor RelA / Q000378:metabolism; D014363:Tryptamines / Q000494:pharmacology; D000099181:Dectin-1
chemical_list: D004268:DNA-Binding Proteins; D037181:Lectins, C-Type; D008550:Melatonin; D009687:Nuclear Proteins; D020569:Proto-Oncogene Proteins c-rel; D013764:Tetrahydronaphthalenes; D051996:Transcription Factor RelA; D014363:Tryptamines; C114459:4-phenyl-2-propionamidotetraline; C546929:CLEC7A protein, human; D000099181:Dectin-1; C068059:REL protein, human; C498143:RELA protein, human; C057154:luzindole
keywords: dectin-1; human colostrum; melatonin; mononuclear cells; nuclear factor kappa B (NF-κB); phagocytosis; zymosan