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Mast cells (MCs) are major effector cells that play a protective role against pathogens and inflammation. MC distribution and activation are associated with the circadian rhythm via two major pathways, IgE\/Fc\u03b5RI\u2010 and IL\u201033\/ST2\u2010mediated signaling. Furthermore, there is a robust oscillation between clock genes and MC\u2010specific genes. Melatonin is a hormone derived from the amino acid tryptophan and is produced primarily in the pineal gland near the center of the brain, and histamine is a biologically active amine synthesized from the decarboxylation of the amino acid histidine by the L\u2010histidine decarboxylase enzyme. Melatonin and histamine are previously reported to modulate circadian rhythms by pathways incorporating various modulators in which the nuclear factor\u2013binding near the \u03ba light\u2010chain gene in B cells, NF\u2010\u03baB, is the common key factor. NF\u2010\u03baB interacts with the core clock genes and disrupts the production of pro\u2010inflammatory cytokine mediators such as IL\u20106, IL\u201013, and TNF\u2010\u03b1. Currently, there has been no study evaluating the interdependence between melatonin and histamine with respect to circadian oscillations in MCs. Accumulating evidence suggests that restoring circadian rhythms in MCs by targeting melatonin and histamine via NF\u2010\u03baB may be promising therapeutic strategy for MC\u2010mediated inflammatory diseases. This review summarizes recent findings for circadian\u2010mediated MC functional roles and activation paradigms, as well as the therapeutic potentials of targeting circadian\u2010mediated melatonin and histamine signaling in MC\u2010dependent inflammatory diseases.<\/jats:p>","DOI":"10.1111\/jpi.12699","type":"journal-article","created":{"date-parts":[[2020,10,5]],"date-time":"2020-10-05T22:54:37Z","timestamp":1601938477000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["The interplay between mast cells, pineal gland, and circadian rhythm: Links between histamine, melatonin, and inflammatory mediators"],"prefix":"10.1111","volume":"70","author":[{"given":"Linh","family":"Pham","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology Department of Medicine Indiana University School of Medicine Indianapolis IN USA"},{"name":"Department of Science and Mathematics Texas A&amp;M University \u2013 Central Texas Killeen TX USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"Baiocchi","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Rome Tor Vergata Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsey","family":"Kennedy","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Department of Medicine Indiana University School of Medicine Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5380-8001","authenticated-orcid":false,"given":"Keisaku","family":"Sato","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Department of Medicine Indiana University School of Medicine Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vik","family":"Meadows","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Department of Medicine Indiana University School of Medicine Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanyin","family":"Meng","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Department of Medicine Indiana University School of Medicine Indianapolis IN USA"},{"name":"Department of Medicine Richard L. 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