Epigenetic regulation of inflammatory gene expression in macrophages by selenium

Vivek Narayan, Kodihalli C. Ravindra, Chang Liao, Naveen Kaushal, Bradley A. Carlson, Kumble Sandeep Prabhu

Research output: Contribution to journalArticle

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Abstract

Acetylation of histone and non-histone proteins by histone acetyltransferases plays a pivotal role in the expression of proinflammatory genes. Given the importance of dietary selenium in mitigating inflammation, we hypothesized that selenium supplementation may regulate inflammatory gene expression at the epigenetic level. The effect of selenium towards histone acetylation was examined in both in vitro and in vivo models of inflammation by chromatin immunoprecipitation assays and immunoblotting. Our results indicated that selenium supplementation, as selenite, decreased acetylation of histone H4 at K12 and K16 in COX-2 and TNFα promoters, and of the p65 subunit of the redox sensitive transcription factor NFκB in primary and immortalized macrophages. On the other hand, selenomethionine had a much weaker effect. Selenite treatment of HIV-1-infected human monocytes also significantly decreased the acetylation of H4 at K12 and K16 on the HIV-1 promoter, supporting the down-regulation of proviral expression by selenium. A similar decrease in histone acetylation was also seen in the colonic extracts of mice treated with dextran sodium sulfate that correlated well with the levels of selenium in the diet. Bone-marrow-derived macrophages from Trsp fl/fl Cre LysM mice that lack expression of selenoproteins in macrophages confirmed the important role of selenoproteins in the inhibition of histone H4 acetylation. Our studies suggest that the ability of selenoproteins to skew the metabolism of arachidonic acid contributes, in part, to their ability to inhibit histone acetylation. In summary, our studies suggest a new role for selenoproteins in the epigenetic modulation of proinflammatory genes.

Original languageEnglish (US)
Pages (from-to)138-145
Number of pages8
JournalJournal of Nutritional Biochemistry
Volume26
Issue number2
DOIs
StatePublished - Feb 1 2015

Fingerprint

Acetylation
Macrophages
Gene Expression Regulation
Selenium
Epigenomics
Gene expression
Selenoproteins
Histones
Selenious Acid
HIV-1
Genes
Selenomethionine
Inflammation
Histone Acetyltransferases
Gene Expression
Dextran Sulfate
Chromatin Immunoprecipitation
Nutrition
Immunoblotting
Arachidonic Acid

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Nutrition and Dietetics
  • Clinical Biochemistry

Cite this

Narayan, Vivek ; Ravindra, Kodihalli C. ; Liao, Chang ; Kaushal, Naveen ; Carlson, Bradley A. ; Prabhu, Kumble Sandeep. / Epigenetic regulation of inflammatory gene expression in macrophages by selenium. In: Journal of Nutritional Biochemistry. 2015 ; Vol. 26, No. 2. pp. 138-145.
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Epigenetic regulation of inflammatory gene expression in macrophages by selenium. / Narayan, Vivek; Ravindra, Kodihalli C.; Liao, Chang; Kaushal, Naveen; Carlson, Bradley A.; Prabhu, Kumble Sandeep.

In: Journal of Nutritional Biochemistry, Vol. 26, No. 2, 01.02.2015, p. 138-145.

Research output: Contribution to journalArticle

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