Galectin-9 Protein Expression in Endothelial Cells Is Positively Regulated by Histone Deacetylase 3

Saydul Alam, Hongling Li, Andriana Margariti, Daniel Martin, Anna Zampetaki, Ouassila Habi, Gillian Cockerill, Yanhua Hu, Qingbo Xu, Lingfang Zeng

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)

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-gamma (IFN-gamma) 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-gamma-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-gamma 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.
Original languageEnglish
Pages (from-to)44211 - 44217
Number of pages7
JournalJournal of Biological Chemistry
Volume286
Issue number51
DOIs
Publication statusPublished - 23 Dec 2011

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