{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:30:11Z","timestamp":1791268211777,"version":"4.1.0"},"reference-count":115,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2013,5,24]],"date-time":"2013-05-24T00:00:00Z","timestamp":1369353600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 \u03ba-light-chain-enhancer of activated B cells (NF-\u03baB) blocks noradrenaline-induced melatonin synthesis in pinealocytes, which induces melatonin synthesis in macrophages. In addition, melatonin reduces NF-\u03baB 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-\u03baB activity leads these cells to a more quiescent state. The opposite effect of NF-\u03baB in pinealocytes and immune competent cells is due to different NF-\u03baB dimers recruited in each phase of the defense response. This coordinated shift of the source of melatonin driven by NF-\u03baB 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.<\/jats:p>","DOI":"10.3390\/ijms140610979","type":"journal-article","created":{"date-parts":[[2013,5,24]],"date-time":"2013-05-24T13:02:03Z","timestamp":1369400523000},"page":"10979-10997","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":110,"title":["Immune-Pineal Axis: Nuclear Factor \u03baB (NF-kB) Mediates the Shift in the Melatonin Source from Pinealocytes to Immune Competent Cells"],"prefix":"10.3390","volume":"14","author":[{"given":"Regina","family":"Markus","sequence":"first","affiliation":[{"name":"Laboratory of Chronopharmacology, Department of Physiology, Institute of Bioscience,  University of S\u00e3o Paulo, S\u00e3o Paulo 05508-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"Cecon","sequence":"additional","affiliation":[{"name":"Laboratory of Chronopharmacology, Department of Physiology, Institute of Bioscience,  University of S\u00e3o Paulo, S\u00e3o Paulo 05508-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Pires-Lapa","sequence":"additional","affiliation":[{"name":"Laboratory of Chronopharmacology, Department of Physiology, Institute of Bioscience,  University of S\u00e3o Paulo, S\u00e3o Paulo 05508-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2013,5,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1007\/BF01923947","article-title":"The melatonin rhythm: Both a clock and a calendar","volume":"49","author":"Reiter","year":"1993","journal-title":"Experientia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1111\/j.1600-079X.2006.00407.x","article-title":"One molecule, many derivatives: A never-ending interaction of melatonin with reactive oxygen and nitrogen species?","volume":"42","author":"Tan","year":"2007","journal-title":"J. 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