{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T15:20:31Z","timestamp":1790522431347,"version":"4.1.0"},"reference-count":56,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2015,3,17]],"date-time":"2015-03-17T00:00:00Z","timestamp":1426550400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Oregon Agricultural Experiment Station","award":["OR00735"],"award-info":[{"award-number":["OR00735"]}]},{"name":"Environmental Health Science Center at Oregon State University","award":["P30 ES00210"],"award-info":[{"award-number":["P30 ES00210"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Nutrition Food Res"],"published-print":{"date-parts":[[2015,5]]},"abstract":"<jats:sec><jats:title>Scope<\/jats:title><jats:p>Zinc deficiency results in immune dysfunction and promotes systemic inflammation. The objective of this study was to examine the effects of zinc deficiency on cellular immune activation and epigenetic mechanisms that promote inflammation. This work is potentially relevant to the aging population given that age\u2010related immune defects, including chronic inflammation, coincide with declining zinc status.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>An in vitro cell culture system and the aged mouse model were used to characterize immune activation and DNA methylation profiles that may contribute to the enhanced proinflammatory response mediated by zinc deficiency. Zinc deficiency upregulated cell activation markers ICAM1, MHC class II, and CD86 in THP1 cells, which coincided with increased IL1\u03b2 and IL6 responses following LPS stimulation. A decreased zinc status in aged mice was similarly associated with increased ICAM1 and IL6 gene expression. Reduced IL6 promoter methylation was observed in zinc\u2010deficient THP1 cells, as well as in aged mice and human lymphoblastoid cell lines derived from aged individuals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Zinc deficiency induced inflammatory response in part by eliciting aberrant immune cell activation and altered promoter methylation. Our results suggested potential interactions between zinc status, epigenetics, and immune function, and how their dysregulation could contribute to chronic inflammation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mnfr.201400761","type":"journal-article","created":{"date-parts":[[2015,2,5]],"date-time":"2015-02-05T14:00:44Z","timestamp":1423144844000},"page":"991-999","source":"Crossref","is-referenced-by-count":160,"title":["Zinc deficiency enhanced inflammatory response by increasing immune cell activation and inducing IL6 promoter demethylation"],"prefix":"10.1002","volume":"59","author":[{"given":"Carmen P.","family":"Wong","sequence":"first","affiliation":[{"name":"School of Biological &amp; Population Health Sciences Oregon State University, Corvallis  OR USA"},{"name":"Linus Pauling Institute Oregon State University  Corvallis OR USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole A.","family":"Rinaldi","sequence":"additional","affiliation":[{"name":"School of Biological &amp; Population Health Sciences Oregon State University, Corvallis  OR USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Ho","sequence":"additional","affiliation":[{"name":"School of Biological &amp; Population Health Sciences Oregon State University, Corvallis  OR USA"},{"name":"Linus Pauling Institute Oregon State University  Corvallis OR USA"},{"name":"Moore Family Center for Whole Grain Foods Nutrition and Preventive Health Oregon State University  Corvallis OR USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,3,17]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.110.005744"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.nutr.24.012003.132454"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/68.2.447S"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.nutr.23.011702.073054"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.20810"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e31819cefe4"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00280.2006"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2012.07.005"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201100511"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/78.4.756"},{"key":"e_1_2_8_12_1","doi-asserted-by":"crossref","first-page":"2260","DOI":"10.1210\/jcem.85.6.6627","article-title":"Blood micronutrient and thyroid hormone concentrations in the oldest\u2010old","volume":"85","author":"Ravaglia G.","year":"2000","journal-title":"J. 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