TitleZinc deficiency enhanced inflammatory response by increasing immune cell activation and inducing IL6 promoter demethylation.
Publication TypeJournal Article
Year of Publication2015
AuthorsWong CP, Rinaldi NA, Ho E
JournalMol Nutr Food Res
Date Published2015 May
KeywordsAging, Animals, Cells, Cultured, DNA Methylation, Female, Humans, Inflammation, Intercellular Adhesion Molecule-1, Interleukin-6, Macrophage Activation, Macrophages, Mice, Mice, Inbred C57BL, Promoter Regions, Genetic, Zinc

SCOPE: 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-related immune defects, including chronic inflammation, coincide with declining zinc status.

METHODS AND RESULTS: 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 IL1β 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-deficient THP1 cells, as well as in aged mice and human lymphoblastoid cell lines derived from aged individuals.

CONCLUSION: 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.

Alternate JournalMol Nutr Food Res
PubMed ID25656040
PubMed Central IDPMC4425307
Grant ListP30 ES000210 / ES / NIEHS NIH HHS / United States
R21 ES023937 / ES / NIEHS NIH HHS / United States
P30 ES00210 / ES / NIEHS NIH HHS / United States