Hydrogen sulfide attenuates cytokine production through the modulation of chromatin remodeling

Hydrogen sulfide (H2S) is an endogenous gaseous biological mediator, which regulates, among others, the oxidative balance of cells under normal physiological conditions, as well as in various diseases. Several previous studies have reported that H2S attenuates inflammatory mediator production. In th...

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Bibliographic Details
Published in:International journal of molecular medicine 2015-06, Vol.35 (6), p.1741-1746
Main Authors: RIOS, ESTER C.S, SZCZESNY, BARTOSZ, SORIANO, FRANCISCO G, OLAH, GABOR, SZABO, CSABA
Format: Article
Language:English
Subjects:
Cell culture
Chromatin
Cytokines
Deoxyribonucleic acid
DNA
DNA methylation
endotoxin
Epigenetics
Experiments
Gene expression
Health aspects
histone deacetylase
Hydrogen sulfide
Immunoglobulins
inflammation
Proteins
Tumor necrosis factor-TNF
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Summary:Hydrogen sulfide (H2S) is an endogenous gaseous biological mediator, which regulates, among others, the oxidative balance of cells under normal physiological conditions, as well as in various diseases. Several previous studies have reported that H2S attenuates inflammatory mediator production. In this study, we investigated the role of H2S in chromatin modulation in an in vitro model of lipopolysaccharide (LPS)-induced inflammation and evaluated its effects on inflammatory cytokine production. Tamm-Horsfall protein 1 (THP-1) differentiated macrophages were pre-treated with sodium hydrosulfide (NaHS) (an H2S donor) at 0.01, 0.1, 0.5 or 1 mM for 30 min. To stimulate cytokine production, the cells were challenged with bacterial LPS (1 μg/ml) for 1, 4, 8 or 24 h. Histone H3 acetylation was analyzed by chromatin immunoprecipitation (ChIP), cytokine production was measured by ELISA and histone deacetylase (HDAC) activity was analyzed using a standard biochemical assay. H2S inhibited the production of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in a concentration-dependent manner; it was most effective at the two highest concentrations used. This effect was associated with a decrease in histone H3 acetylation at the IL-6 and TNF-α promoters in the cells exposed to H2S or H2S + LPS. The findings of the present study suggest that H2S suppresses histone acetylation, which, in turn, inhibits chromatin openness, leading to a decrease in the gene transcription of various pro-inflammatory cytokines. Therefore, this mechanism may contribute to the previously demonstrated anti-inflammatory effects of H2S and various H2S donors.
ISSN:1107-3756
1791-244X
DOI:10.3892/ijmm.2015.2176