{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T16:27:12Z","timestamp":1776961632093,"version":"3.51.4"},"reference-count":54,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2012,2,21]],"date-time":"2012-02-21T00:00:00Z","timestamp":1329782400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2012,2,21]],"date-time":"2012-02-21T00:00:00Z","timestamp":1329782400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Pineal Research"],"published-print":{"date-parts":[[2012,9]]},"abstract":"<jats:p>\n                    <jats:bold>Abstract:\u2002<\/jats:bold>\n                    Melatonin is an indoleamine secreted by the pineal gland as well as a plant\u2010derived product that exerts potential anti\u2010inflammatory properties, but the mechanisms of action remain unclear. Here, we investigated the roles of melatonin in regulation of proinflammatory mediators and identified the underlying mechanisms in human vascular smooth muscle (VSM) cell line CRL1999 stimulated by lipopolysaccharide (LPS). We found that treatment with melatonin significantly inhibited the production and expression of TNF\u2010\u03b1 and interleukin (IL)\u20101\u03b2, cyclooxygenase\u20102 (COX\u20102), inducible nitric oxide synthase, prostaglandin E(2) (PGE2), and nitric oxide (NO) in a dose\u2010dependent manner. Moreover, we also found that the suppression of proinflammatory mediators by melatonin was mediated through inhibition of MAPK, NF\u2010\u03baB, c\/EBP\u03b2, and p300 signaling in LPS\u2010stimulated CRL1999 cells. Treatment with melatonin markedly inhibited phosphorylation of ERK1\/2, JNK, p38 MAPK, I\u03baB\u2010\u03b1, and c\/EBP\u03b2, blocked binding of NF\u2010\u03baB and c\/EBP\u03b2 to promoters, and suppressed p300 histone acetyltransferase (HAT) activity and p300 HAT\u2010mediated NF\u2010\u03baB acetylation. Transfection with an ERK\u2010, I\u03baB\u2010, or c\/EBP\u03b2\u2010specific siRNA or pretreatment with an ERK\u2010, p38 MAPK\u2010, or p300\u2010selective inhibitor considerably abrogated the melatonin\u2010mediated inhibition of proinflammatory mediators. Conversely, exogenous overexpression of a constitutively active p300, but not its HAT mutant, effectively reversed the melatonin\u2010mediated inhibitions. Collectively, these results indicate that melatonin suppresses proinflammatory mediators by simultaneously targeting the multiple signaling such as ERK\/p38 MAPK, c\/EBP\u03b2, NF\u2010\u03baB, and p300, in LPS\u2010stimulated VSM cell line CRL1999, and suggest that melatonin is a potential candidate compound for the treatment of proinflammatory disorders.\n                  <\/jats:p>","DOI":"10.1111\/j.1600-079x.2012.00982.x","type":"journal-article","created":{"date-parts":[[2012,1,30]],"date-time":"2012-01-30T15:30:00Z","timestamp":1327937400000},"page":"154-165","source":"Crossref","is-referenced-by-count":92,"title":["RETRACTED: Melatonin suppresses proinflammatory mediators in lipopolysaccharide\u2010stimulated CRL1999 cells via targeting MAPK, NF\u2010\u03baB, c\/EBP\u03b2, and p300 signaling"],"prefix":"10.1111","volume":"53","author":[{"given":"Dingbo","family":"Shi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangsheng","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingshu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liqun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wangbing","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lingyi","family":"Fu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fangyun","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenlin","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wuguo","family":"Deng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,2,21]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2011.00884.x"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2011.00916.x"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2010.00749.x"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-185X.2009.00118.x"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2010.04.008"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2011.00899.x"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-010-1364-5"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-079X.2009.00699.x"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-006-9353-x"},{"key":"e_1_2_6_11_2","first-page":"683","article-title":"Antioxidative 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