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| TSA Down-regulated Expression of IDO in HepG2 Human Liver Cells by Inhibiting STAT1 Phosphorylation and Nuclear Translocation |
| LI Ling-ling, JIANG Guan-min, ZHANG Ge, YI Yan-mei, ZHANG Fan, DU Jun |
| Laboratory of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China |
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Abstract Objective: To study the molecular mechanism of TSA-induced indoleamine 2, 3-dioxygenase (IDO) downregulation in human liver cancer cell line HepG2. Methods: The roles of TSA on the IFN-γ induced IDO expression in HepG2 cell, the phosphorylation of signal transducer and activator of transcription 1 (STAT1) and the activation of interferon regulatory factor 1 (IRF-1) were examined by western blotting. IDO expression in TSA-treated HepG2 cells was also detected by immunocytochemistry, and changes in the expression of IFN-γ receptor 2 was analyzed by Flow cytometry. Effect of TSA on STAT1 nuclear translocation was observed by a confocal laser-scanning microscope. The Luciferase activity of the activation of γ-interferon activated sites (GAS), interferon stimulated response element (ISRE) and nuclear factor-κB (NF-κB) was measured by Dual Luciferase Reporter Assay System. Results: TSA dose-dependently reduced IFN-γ induced IDO expression, and inhibited STAT1 phosphorylation at Tyr-701 and nuclear translocation in HepG2 cell,but it upregulated the expression of IFN-γ receptor 2. Dual luciferase reporter assay and Western blotting results showed that TSA blocked IFN-γ-induced activation of GAS and IRF-1, but not NF-κB and ISRE. Conclusion: TSA can down-regulated IFN-γ induced IDO expression in HepG2 cell, which may be associated with the repression of phosphorylation and nuclear translocation of STAT1 and its binding to GAS, not due to reduced expression of the IFN-γ receptor.
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Received: 16 May 2011
Published: 25 September 2011
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