Galectin-9 protein expression in endothelial cells is positively regulated by histone deacetylase 3

J Biol Chem. 2011 Dec 23;286(51):44211-44217. doi: 10.1074/jbc.M111.242289. Epub 2011 Oct 25.

Abstract

Galectin-9 expression in endothelial cells can be induced in response to inflammation. However, the mechanism of its expression remains unclear. In this study, we found that interferon-γ (IFN-γ) induced galectin-9 expression in human endothelial cells in a time-dependent manner, which coincided with the activation of histone deacetylase (HDAC). When endothelial cells were treated with the HDAC3 inhibitor, apicidin, or shRNA-HDAC3 knockdown, IFN-γ-induced galectin-9 expression was abolished. Overexpression of HDAC3 induced the interaction between phosphoinositol 3-kinase (PI3K) and IFN response factor 3 (IRF3), leading to IRF3 phosphorylation, nuclear translocation, and galectin-9 expression. HDAC3 functioned as a scaffold protein for PI3K/IRF3 interaction. In addition to galectin-9 expression, IFN-γ also induced galectin-9 location onto plasma membrane, which was HDAC3-independent. Importantly, HDAC3 was essential for the constitutive transcription of PI3K and IRF3, which might be responsible for the basal level of galectin-9 expression. The phosphorylation of IRF3 was essential for galectin-9 expression. This study provides new evidence that HDAC3 regulates galectin-9 expression in endothelial cells via interaction with PI3K-IRF3 signal pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Endothelial Cells / cytology*
  • Endothelial Cells / metabolism*
  • Galectins / metabolism*
  • Gene Expression Regulation, Enzymologic*
  • Histone Deacetylases / metabolism*
  • Humans
  • Inflammation
  • Interferon Regulatory Factor-3 / metabolism
  • Interferon-gamma / metabolism
  • Interferons / metabolism
  • Models, Biological
  • Phosphatidylinositol 3-Kinases / metabolism
  • Signal Transduction
  • Subcellular Fractions / metabolism

Substances

  • Galectins
  • Interferon Regulatory Factor-3
  • LGALS9 protein, human
  • Interferon-gamma
  • Interferons
  • Phosphatidylinositol 3-Kinases
  • Histone Deacetylases
  • histone deacetylase 3