title: Immune-pineal axis: nuclear factor κB (NF-kB) mediates the shift in the melatonin source from pinealocytes to immune competent cells.
abstract: Pineal gland melatonin is the darkness hormone, while extra-pineal melatonin produced by the gonads, gut, retina, and immune competent cells acts as a paracrine or autocrine mediator. The well-known immunomodulatory effect of melatonin is observed either as an endocrine, a paracrine or an autocrine response. In mammals, nuclear translocation of nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) blocks noradrenaline-induced melatonin synthesis in pinealocytes, which induces melatonin synthesis in macrophages. In addition, melatonin reduces NF-κB activation in pinealocytes and immune competent cells. Therefore, pathogen- or danger-associated molecular patterns transiently switch the synthesis of melatonin from pinealocytes to immune competent cells, and as the response progresses melatonin inhibition of NF-κB activity leads these cells to a more quiescent state. The opposite effect of NF-κB in pinealocytes and immune competent cells is due to different NF-κB dimers recruited in each phase of the defense response. This coordinated shift of the source of melatonin driven by NF-κB is called the immune-pineal axis. Finally, we discuss how this concept might be relevant to a better understanding of pathological conditions with impaired melatonin rhythms and hope it opens new horizons for the research of side effects of melatonin-based therapies.
authors.affiliation: Laboratory of Chronopharmacology, Department of Physiology, Institute of Bioscience, University of São Paulo, São Paulo 05508-900, Brazil. rpmarkus@usp.br.
authors.forename: Regina P
authors.initials: RP
authors.lastname: Markus
authors.forename: Erika
authors.initials: E
authors.lastname: Cecon
authors.forename: Marco Antonio
authors.initials: MA
authors.lastname: Pires-Lapa
mesh_terms: D000818:Animals; D006801:Humans; D007107:Immune System / Q000166:cytology* / Q000378:metabolism*; D008550:Melatonin / Q000096:biosynthesis / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D010870:Pineal Gland / Q000166:cytology* / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D016328:NF-kappa B; D008550:Melatonin