Zinc deficiency enhanced inflammatory response by increasing immune cell activation and inducing IL6 promoter demethylation
Version of Record online: 17 MAR 2015
© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Volume 59, Issue 5, pages 991–999, May 2015
How to Cite
Wong, C. P., Rinaldi, N. A. and Ho, E. (2015), Zinc deficiency enhanced inflammatory response by increasing immune cell activation and inducing IL6 promoter demethylation. Mol. Nutr. Food Res., 59: 991–999. doi: 10.1002/mnfr.201400761
- Issue online: 5 MAY 2015
- Version of Record online: 17 MAR 2015
- Accepted manuscript online: 5 FEB 2015 08:41AM EST
- Manuscript Accepted: 29 JAN 2015
- Manuscript Revised: 26 JAN 2015
- Manuscript Received: 21 OCT 2014
- Oregon Agricultural Experiment Station. Grant Number: OR00735
- Environmental Health Science Center at Oregon State University. Grant Number: P30 ES00210
- DNA methylation;
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.
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.