Hydrogen sulfide attenuates cytokine production through the modulation of chromatin remodeling

Ester C S Rios, Bartosz Szczesny, Francisco G. Soriano, Gabor Olah, Csaba Szabo

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Hydrogen sulfide (H<inf>2</inf>S) 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 H<inf>2</inf>S attenuates inflammatory mediator production. In this study, we investigated the role of H<inf>2</inf>S 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 withsodium hydrosulfide (NaHS) (an H<inf>2</inf>S 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. H<inf>2</inf>S inhibited the production of interleukin-6 (IL-6) and tumor necrosis factor-A (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 H<inf>2</inf>S or H<inf>2</inf>S + LPS. The findings of the present study suggest that H<inf>2</inf>S 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 H<inf>2</inf>S and various H<inf>2</inf>S donors.

Original languageEnglish (US)
Pages (from-to)1741-1746
Number of pages6
JournalInternational Journal of Molecular Medicine
Volume35
Issue number6
DOIs
StatePublished - Jun 1 2015

Fingerprint

Hydrogen Sulfide
Chromatin Assembly and Disassembly
Acetylation
Histones
Cytokines
Lipopolysaccharides
Chromatin
Interleukin-6
Gasotransmitters
Tumor Necrosis Factor-alpha
Uromodulin
Histone Deacetylases
Chromatin Immunoprecipitation
Anti-Inflammatory Agents
Enzyme-Linked Immunosorbent Assay
Macrophages
Inflammation
Genes

Keywords

  • Endotoxin
  • Histone deacetylase
  • Hydrogen sulfide
  • Inflammation

ASJC Scopus subject areas

  • Genetics

Cite this

Hydrogen sulfide attenuates cytokine production through the modulation of chromatin remodeling. / Rios, Ester C S; Szczesny, Bartosz; Soriano, Francisco G.; Olah, Gabor; Szabo, Csaba.

In: International Journal of Molecular Medicine, Vol. 35, No. 6, 01.06.2015, p. 1741-1746.

Research output: Contribution to journalArticle

Rios, Ester C S ; Szczesny, Bartosz ; Soriano, Francisco G. ; Olah, Gabor ; Szabo, Csaba. / Hydrogen sulfide attenuates cytokine production through the modulation of chromatin remodeling. In: International Journal of Molecular Medicine. 2015 ; Vol. 35, No. 6. pp. 1741-1746.
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