Effect of pioglitazone on balance of regulatory and effector T cells of ure-mic apolipoprotein E knockout mice in vitro / 中国病理生理杂志

ABSTRACT

AIM:To investigate the effects of pioglitazone on the quantity and function-related factors of regu-latory 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 ( 2μmol/L and 20μmol/L) of pioglitazone and PPARγantagonist GW9662 (5μmol/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 de-termined by flow cytometry.The mRNA expressions of Foxp3 and IFNγwas detected by real-time fluorescent quantitative PCR.RESULTS:In vitro, oxLDL induced a Treg/Teff imbalance in splenocytes from the uremic mice.Pioglitazone up-regulated 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 IFNγin the presence or ab-sence of oxLDL, which was reversed by GW9662.CONCLUSION:oxLDL induces a Treg/Teff imbalance in uremic apo-lipoprotein E knockout mice.Pioglitazone modulates the Treg/Teff imbalance probably through PPARγ-independent and-dependent mechanisms.