Li Qing, Wang Yiping, Li Hongqi, Shen Guodong, Hu Shilian
The Central Laboratory of Medical Research Center, The Affiliated Provincial Hospital of Anhui Medical University, Hefei, China.
Cell Physiol Biochem. 2014;33(6):1849-62. doi: 10.1159/000362963. Epub 2014 Jun 20.
CD4(+)CD25(+) regulatory T (Treg) cells and T-helper 17 (Th17) cells play important roles in acute cerebral infarction (ACI). Our previous findings have suggested that oxidized low-density lipoprotein (Ox-LDL) could influence Treg/Th17 ratio in ACI patients. However, the mechanisms are still not clear.
We evaluated the effects of ox-LDL on Th17/Treg cell apoptosis and proliferation in vitro. Our results demonstrated that with increased ox-LDL concentrations, the frequency and suppressive function of Treg cells was decreased while the frequency of Th17 cells was elevated in control subjects. In addition, AnnexinV(+) apoptotic rate, Fas/Fas ligand (FasL) expression, and Caspase-3 activity were escalated in Treg cells while were no significant changes in Th17 cells. Simultaneously, 5-Bromo-29-Deoxyuridine (BrdU) and 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyl Tetrazolium Bromide (MTT) incorporation of Th17 cells was elevated accompanied by upregulated nuclear factor-κB (NF-κB) activity. However, Th17 proliferation was decreased when pre-incubated with Pyrrolidine dithiocarbamate (PDTC, inhibitor of NF-κB activation). Furthermore, there were significant changes induced by ox-LDL in Treg apoptosis, Fas/FasL/Caspase-3 expression of Treg cells, and Th17 proliferation, NF-κB activation of Th17 in ACI patients than in patients with transient ischemic attack (TIA) and control subjects (P<0.01, P<0.05 respectively).
These data support that ox-LDL may influence the Th17/Treg balance by modulating Fasmediated Treg apoptosis and NF-κB-associated Th17 proliferation. Ox-LDL also induced a more significant alteration of Treg and Th17 in ACI patients than in TIA and control groups, suggesting a novel role in the pathogenesis of ACI.
CD4(+)CD25(+)调节性T（Treg）细胞和辅助性T细胞17（Th17）细胞在急性脑梗死（ACI）中起重要作用。我们之前的研究结果表明，氧化型低密度脂蛋白（Ox-LDL）可能会影响ACI患者的Treg/Th17比值。然而，其机制仍不清楚。
我们在体外评估了氧化型低密度脂蛋白对Th17/Treg细胞凋亡和增殖的影响。我们的结果表明，随着氧化型低密度脂蛋白浓度的增加，对照组中Treg细胞的频率和抑制功能降低，而Th17细胞的频率升高。此外，Treg细胞中膜联蛋白V（AnnexinV）(+)凋亡率、Fas/Fas配体（FasL）表达和半胱天冬酶-3（Caspase-3）活性升高，而Th17细胞中无显著变化。同时，Th17细胞的5-溴-2'-脱氧尿苷（BrdU）和噻唑蓝（MTT）掺入量升高，同时核因子-κB（NF-κB）活性上调。然而，用吡咯烷二硫代氨基甲酸盐（PDTC，NF-κB激活抑制剂）预孵育后，Th17细胞增殖减少。此外，与短暂性脑缺血发作（TIA）患者和对照组相比，氧化型低密度脂蛋白在ACI患者的Treg细胞凋亡、Treg细胞的Fas/FasL/Caspase-3表达以及Th17细胞增殖、Th17细胞的NF-κB激活方面引起了显著变化（分别为P<0.01，P<0.05）。
这些数据支持氧化型低密度脂蛋白可能通过调节Fas介导的Treg细胞凋亡和NF-κB相关的Th17细胞增殖来影响Th17/Treg平衡。与TIA和对照组相比，氧化型低密度脂蛋白在ACI患者中还诱导了Treg和Th17细胞更显著的改变，提示其在ACI发病机制中的新作用。
