{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:52:56Z","timestamp":1790697176681,"version":"4.1.0"},"reference-count":66,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,8,19]],"date-time":"2019-08-19T00:00:00Z","timestamp":1566172800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2019,8,19]],"date-time":"2019-08-19T00:00:00Z","timestamp":1566172800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Pineal Research"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Melatonin is the main secretory product of the pineal gland, and it is involved in the regulation of periodic events. A melatonin production independent of the photoperiod is typical of the gut. However, the local physiological role of melatonin at the intestinal tract is poorly characterized. In this study, we evaluated the anti\u2010inflammatory activities of melatonin in an\n                    <jats:italic>in vitro<\/jats:italic>\n                    model of inflamed intestinal epithelium. To this purpose, we assessed different parameters usually associated with intestinal inflammation using IL\u20101\u03b2\u2010stimulated Caco\u20102 cells. Differentiated monolayers of Caco\u20102 cells were preincubated with melatonin (1\u00a0nmol\/L\u201050\u00a0\u03bcmol\/L) and then exposed to IL\u20101\u03b2. After each treatment, different inflammatory mediators, DNA\u2010breakage, and global DNA methylation status were assayed. To evaluate the involvement of melatonin membrane receptors, we also exposed differentiated monolayers to melatonin in the presence of luzindole, a MT1 and MT2 antagonist. Our results showed that melatonin, at concentrations similar to those obtained in the lumen gut after ingestion of dietary supplements for the treatment of sleep disorders, was able to attenuate the inflammatory response induced by IL\u20101\u03b2. Anti\u2010inflammatory effects were expressed as both a decrease of the levels of inflammatory mediators, including IL\u20106, IL\u20108, COX\u20102, and NO, and a reduced increase in paracellular permeability. Moreover, the protection was associated with a reduced NF\u2010\u03baB activation and a prevention of DNA demethylation. Conversely, luzindole did not reverse the melatonin inhibition of stimulated\u2010IL\u20106 release. In conclusion, our findings suggest that melatonin, through a local action, can modulate inflammatory processes at the intestinal level, offering new opportunities for a multimodal management of IBD.\n                  <\/jats:p>","DOI":"10.1111\/jpi.12598","type":"journal-article","created":{"date-parts":[[2019,7,26]],"date-time":"2019-07-26T17:06:10Z","timestamp":1564160770000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":95,"title":["Melatonin reduces inflammatory response in human intestinal epithelial cells stimulated by interleukin\u20101\u03b2"],"prefix":"10.1111","volume":"67","author":[{"given":"Giuseppe","family":"Mannino","sequence":"first","affiliation":[{"name":"Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF) University of Palermo Palermo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Caradonna","sequence":"additional","affiliation":[{"name":"Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF) University of Palermo Palermo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilenia","family":"Cruciata","sequence":"additional","affiliation":[{"name":"Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF) University of Palermo Palermo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonino","family":"Lauria","sequence":"additional","affiliation":[{"name":"Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF) University of Palermo Palermo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Perrone","sequence":"additional","affiliation":[{"name":"Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF) University of Palermo Palermo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5861-3342","authenticated-orcid":false,"given":"Carla","family":"Gentile","sequence":"additional","affiliation":[{"name":"Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF) University of Palermo Palermo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,8,19]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.2174\/1568026615666150220120946"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-079X.2003.00032.x"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00216-010-3653-4"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-079X.2003.02112.x"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-079x.2000.280102.x"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1159\/000109107"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10787-018-0523-8"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-079X.2001.300101.x"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2016.11.031"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-013-2115-z"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1155\/MI.2005.185"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2006.00378.x"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-013-2831-6"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-016-1214-x"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12075"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2004.07.015"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-8981(98)00060-6"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00394-011-0220-5"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00394-014-0760-6"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(00)00160-X"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.2600790604"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrestox.7b00269"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2009.12.010"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2012.914"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-017-1124-5"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/js950267"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.3109\/1061186X.2015.1035275"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00394-012-0414-5"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2010.04.002"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2010.00777.x"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1159\/000123997"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2009.07.001"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-61-6-1214"},{"key":"e_1_2_6_35_1","unstructured":"GebhardtS LemarL HaytowitzD PehrssonP NickleM ShowellB HoldenJ.USDA national nutrient database for standard reference release 21.2008. United States Department of AgricultureAgricultural Research Service."},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micron.2013.12.003"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr060433m"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2012.08.004"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1080\/09629350120054536"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2003.11.046"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.1999.tb00611.x"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.12.9.685"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2008.00657.x"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.3109\/10715762.2013.845295"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0024-3205(97)00008-8"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2005.10.009"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v9.i6.1307"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1042\/bss0730165"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199704103361506"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-12-0147"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.11.6164"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004836-200204000-00003"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.7.4641"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12013"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1159\/000109490"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12019"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2010.00757.x"},{"issue":"3","key":"e_1_2_6_58_1","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1016\/S0022-3565(25)22188-7","article-title":"Luzindole (N\u20100774): a novel melatonin receptor antagonist","volume":"246","author":"Dubocovich ML","year":"1988","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_6_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0703130"},{"key":"e_1_2_6_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2004.09.007"},{"issue":"10","key":"e_1_2_6_61_1","first-page":"2403","article-title":"Oxidative stress and DNA damage: implications in inflammatory bowel disease","volume":"21","author":"Pereira C","year":"2015","journal-title":"Inflamm Bowel Dis"},{"key":"e_1_2_6_62_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu8120785"},{"key":"e_1_2_6_63_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/982639"},{"key":"e_1_2_6_64_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-94-007-4525-4_27"},{"key":"e_1_2_6_65_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39792"},{"key":"e_1_2_6_66_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00079.2004"},{"key":"e_1_2_6_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2004.04.030"}],"container-title":["Journal of Pineal Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jpi.12598","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jpi.12598","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jpi.12598","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:10:16Z","timestamp":1784679016000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jpi.12598"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,19]]},"references-count":66,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2019,10]]}},"alternative-id":["10.1111\/jpi.12598"],"URL":"https:\/\/doi.org\/10.1111\/jpi.12598","archive":["Portico"],"relation":{},"ISSN":["0742-3098","1600-079X"],"issn-type":[{"value":"0742-3098","type":"print"},{"value":"1600-079X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,8,19]]},"assertion":[{"value":"2019-04-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-07-16","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-08-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e12598"}}