Sodium butyrate inhibits interferon-gamma induced indoleamine 2,3-dioxygenase expression via STAT1 in nasopharyngeal carcinoma cells
Aims Indoleamine 2, 3-dioxygenase (IDO) inhibits T-cell proliferation by catalyzing the conversion of L-tryptophan to L-kynurenine.IDO-induced immune tolerance weakens the clinical outcomes of immunotherapies.Sodium butyrate (NaB), one of the histone deacetylase inhibitors (HDACIs), has potential anti-tumor effects.Our previous studies revealed that NaB could inhibit IFN-γ induced IDO expression in nasopharyngeal carcinoma cells, CNE2.In the present study, we aim to investigate to the mechanism of NaB interfering with the interferon-gamma (IFN-γ)-mediated IDO expression signaling transduction.Main methods IDO expression and STAT1 phosphorylation in CNE2 cells were analyzed by Western blotting, STAT1 acetylation was evaluated by immunoprecipitation.STAT1 nuclear translocation and NF-κB activity were detected by transient transfection and reporter gene assay.Key findings we found that NAB inhibited IFN-γ-induced IDO expression in CNE2 cells via decreasing phosphorylation and nuclear translocation of STAT1, but not via down-regulation of IFN-γ-receptor (IFNGR).Immunoprecipitation assays revealed that NAB increased STAT1 acetylation.Furthermore, NaB elevated the activity of NF-κB in CNE2 cells, and blocking the NF-κB activity had no effect on the IFN-γ-induced IDO expression.Significance These results suggest that NaB inhibited IFN-γ-induced IDO expression via STAT1 increased acetylation, decreased phosphorylation, and reduced nuclear translocation.These provided new evidences for the anti-tumor action of NaB and potential drug targets to reduce the IDO-induced immune tolerance.
Indoleamine 2,3-dioxygenase Sodium butyrate STAT1
Yu-Wen He Hong-Sheng Wang Jun zeng Xiefan Fang Hong-Yuan Chen Jun Du Xin-yun Yang
Department of Pharmacy,the First Affiliated Hospital of Guangzhou Medical University,Guangzhou Medic Department of Microbial and Biochemical Pharmacy,School of Pharmaceutical Sciences,Sun Yat-sen Unive Child Health Research Institute,Department of Pediatrics,College of Medicine,University of Florida,G
国内会议
广州
英文
1-7
2014-01-11（万方平台首次上网日期，不代表论文的发表时间）