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Effect of pioglitazone on balance of regulatory and effector T cells of uremic apolipoprotein E knockout mice in vitro
Authors:SHEN Yan  XIAO Yan  WANG Li-jun  ZHAO Yan  TIAN Yu-ling  LIANG Xiao  YIN Ai-ping
Institution:1. Department of Nephrology, Center of Nephrology, Medical School of Xi'an Jiaotong University, Xi'an 710061, China; 2. Department of Cardiovascular Medicine, The First Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an 710061, China; 3. Key Laboratory of Ministry of Education for Environment and Genes Related to Diseases, Xi'an Jiaotong University, Xi'an 710061, China
Abstract:AIM: To investigate the effects of pioglitazone on the quantity and function-related factors of regulatory and effector T cells (Treg and Teff ) of uremic apolipoprotein E knockout mice in vitro with or without the stimulation of atherosclerotic plaque-specific antigen oxidized low-density lipoprotein (oxLDL). METHODS: Uremic apolipoprotein E knockout mouse model was established by 2-step surgical procedure. After intervention with different concentrations (2 μmol/L and 20 μmol/L) of pioglitazone and PPARγ antagonist GW9662 (5 μmol/L) on splenocytes of uremic mice for 12 h in the presence or absence of oxLDL (2 mg/L), the levels of CD4+ CD25+ Foxp3+ Treg and IFNγ+ CD4+ Teff were determined by flow cytometry. The mRNA expressions of Foxp3 and IFNγ was detected by real-time fluorescent quantitative PCR. RESULTS: In vitro, oxLDL induced a Treg/Teff imbalance in splenocytes from the uremic mice. Pioglitazone upregulated the level of Treg and mRNA expression of Foxp3 in the presence of oxLDL, which was not antagonized by GW9662. Meanwhile, pioglitazone downregulated the level of Teff and mRNA expression of IFNγ in the presence or absence of oxLDL, which was reversed by GW9662. CONCLUSION: oxLDL induces a Treg/Teff imbalance in uremic apolipoprotein E knockout mice. Pioglitazone modulates the Treg/Teff imbalance probably through PPARγ-independent and-dependent mechanisms.
Keywords:Pioglitazone  Peroxisome proliferator-activated receptor γ  Uremia  Regulatory T cells  Effector T cells  
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