title: Oxidative stress regulates IL-4 gene expression in mast cells through the reduction of histone deacetylase.
abstract: OBJECTIVE
  Many proinflammatory cytokines are regulated by the acetylation and deacetylation of the core histone. Since dysregulation of T helper 2 cytokine production is a key in the pathogenesis of allergic diseases, we examined the role of histone deacetylase (HDAC) on interleukin (IL)-4 gene expression in mast cells. We also examined whether oxidative stress has any impact on HDAC activity.
  
  
  METHODS
  In vitro study.
  
  
  METHODS
  Academic research laboratory.
  
  
  METHODS
  An IgE-sensitized mast cell line (RBL-2H3 cells) was treated with varying concentrations of the HDAC inhibitors trichostatin A (TSA) and H2O2 and stimulated with antigens. The amount of IL-4 gene expression was quantified by real-time polymerase chain reaction. Quantitative measurement of IL-4 in the cell supernatant was performed using enzyme-linked immunosorbent assay. Moreover, HDAC activity was measured with the use of a nonisotopic assay that utilized an HDAC Fluorescent Activity Assay Kit.
  
  
  RESULTS
  IL-4 mRNA expression was induced by antigens in IgE-sensitized RBL-2H3 cells. Pretreatment with TSA and H2O2 enhanced IL-4 mRNA expression up to 5-fold in a dose-dependent manner. Furthermore, HDAC activity in RBL-2H3 cells was reduced after treatment with H2O2.
  
  
  CONCLUSIONS
  Our results suggest that oxidative stress may up-regulate IL-4 gene expression in mast cells via a decrease in HDAC activity.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan nmaru@med.hokudai.ac.jp.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nakamaru
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Dai
authors.initials: D
authors.lastname: Takagi
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Homma
authors.affiliation: Department of Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Shigetsugu
authors.initials: S
authors.lastname: Hatakeyama
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fukuda
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation; D006655:Histone Deacetylases / Q000378:metabolism*; D015847:Interleukin-4 / Q000235:genetics*; D008407:Mast Cells / Q000276:immunology; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D051381:Rats
chemical_list: D015847:Interleukin-4; D006655:Histone Deacetylases
keywords: histone deacetylase; interleukin (IL)–4; mast cell; oxidative stress