{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T21:17:09Z","timestamp":1791494229435,"version":"4.3.4"},"reference-count":50,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,12,5]],"date-time":"2016-12-05T00:00:00Z","timestamp":1480896000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The accumulation of macrophages has been observed around lesions of the brain in patients with Minamata disease. In this condition, mercury has been detected histochemically in macrophages throughout the brain. However, the role of macrophages in the neurotoxicity of methylmercury (MeHg) and the molecular mechanisms of their response to MeHg exposure remain to be elucidated. Here, we investigated how MeHg affects the expression of proinflammatory cytokines such as interleukin (IL)\u20106 and IL\u20108 in cultured human U937 macrophages. Compared with controls, IL\u20106 and IL\u20108 mRNA expression was maximally induced in U937 macrophages after treatment with 10\u2009\u03bcM MeHg for 6\u2009h. The protein secretion of IL\u20106 and IL\u20108 was significantly stimulated by MeHg in U937 macrophages. Results from luciferase reporter assay indicated functional activation of nuclear factor kappa B and the involvement of subunit RelA and p50 in MeHg\u2010induced IL\u20106 and IL\u20108 activation, which was confirmed by siRNA knockdown experiments. MeHg exposure at 4\u2009\u03bcM also significantly induced IL\u20108 expression in U\u201087 MG cells at mRNA and protein level, indicating that IL\u20108 induction might be a general mode of action of MeHg treatment among different cell types. These results indicate a possible involvement of an early inflammatory response, including IL\u20106 and IL\u20108 expression in the pathogenesis of MeHg. <jats:italic>N<\/jats:italic>\u2010acetyl\u2010<jats:sc>l<\/jats:sc>\u2010cysteine suppressed MeHg\u2010induced activation of IL\u20106 and IL\u20108 mRNA expression in U937 macrophages, indicating the effectiveness of <jats:italic>N<\/jats:italic>\u2010acetyl\u2010<jats:sc>l<\/jats:sc>\u2010cysteine as a therapeutic drug in MeHg\u2010induced inflammation. Copyright \u00a9 2016 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/jat.3411","type":"journal-article","created":{"date-parts":[[2016,12,5]],"date-time":"2016-12-05T01:13:17Z","timestamp":1480900397000},"page":"611-620","source":"Crossref","is-referenced-by-count":26,"title":["Activation of interleukin\u20106 and \u20108 expressions by methylmercury in human U937 macrophages involves RelA and p50"],"prefix":"10.1002","volume":"37","author":[{"given":"Megumi","family":"Yamamoto","sequence":"first","affiliation":[{"name":"Integrated Physiology Section, Department of Basic Medical Science National Institute for Minamata Disease  4058\u201018 Hama Minamata, Kumamoto 867\u20100008 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noureen","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Preventive Medicine Kagoshima University Graduate School of Medical and Dental Sciences  8\u201035\u20101 Sakuragaoka Kagoshima 890\u20108544 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muflihatul","family":"Muniroh","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Preventive Medicine Kagoshima University Graduate School of Medical and Dental Sciences  8\u201035\u20101 Sakuragaoka Kagoshima 890\u20108544 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eriko","family":"Motomura","sequence":"additional","affiliation":[{"name":"Integrated Physiology Section, Department of Basic Medical Science National Institute for Minamata Disease  4058\u201018 Hama Minamata, Kumamoto 867\u20100008 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rie","family":"Yanagisawa","sequence":"additional","affiliation":[{"name":"Integrated Physiology Section, Department of Basic Medical Science National Institute for Minamata Disease  4058\u201018 Hama Minamata, Kumamoto 867\u20100008 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takami","family":"Matsuyama","sequence":"additional","affiliation":[{"name":"Department of Immunology Kagoshima University Graduate School of Medical and Dental Sciences  8\u201035\u20101 Sakuragaoka Kagoshima 890\u20108544 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph F. 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