Effect of environmental chemicals on the Th1/Th2 development and exacerbation of airway hyperresponsiveness

本研究探讨了环境化学物质干扰Th 1/Th 2平衡的机制。在这里，我们表明，环境化学品降低细胞内GSH水平和N-乙酰-L-半胱氨酸的GSH水平的强制增加减弱环境化学品的影响，干扰Th 1/Th 2的发展从幼稚的CD 4 + T细胞。此外，使用一个显着的污染物，TBT，我们表明，Th 1克隆比Th 2克隆TBT诱导的细胞凋亡所定义的膜联蛋白V结合磷脂酰丝氨酸残基更敏感。流式细胞仪检测结果显示，TBT处理后，Th 1细胞产生的H_2O_2水平高于Th 2细胞。细胞内GSH基础水平与TBT诱导的H_2O_2产生量的增加呈负相关。这些结果表明，TBT更容易诱导Th 1细胞凋亡，通过产生ROS，由于低GSH水平，TBT可能有助于放大的Th 2优势。我们推测，较低的GSH在Th 1细胞的基础水平是重要的因素，决定了TBT诱导的细胞凋亡的Th 1细胞的易感性。基于我们在这里和以前提出的数据，我们提出了一种新的机制，通过这种机制，环境污染物通过选择性诱导分化的Th 1细胞凋亡诱导Th 2优势，以及从幼稚的CD 4 + T细胞的Th 1/Th 2分化的调制，导致过敏性疾病的患病率增加。

In this study, we have investigated the mechanisms of environmental chemicals to disturb Th1/Th2 balance. Here we show that environmental chemicals reduce intracellular GSH levels and forced increase in GSH levels by N-acetyl-L-Cysteine attenuate the effect of environmental chemicals to disturb Th1/Th2 development from naive CD4+ T cells. Furthermore, using one of the notable pollutant, TBT, we show that Th1 clones were more susceptible than Th2 clones to the TBT-induced apoptosis as defined by Annexin V binding to phosphatidylserine residues. Flow cytometry showed that Th1 clones generated higher level of intracellular H_2O_2 in response to TBT treatment than Th2 clones. An inverse correlation between basal levels of intracellular GSH and TBT-induced increase in H_2O_2 generation was observed. These results suggest that TBT more easily induce Th1 apoptosis via generation of ROS, due to the low GSH level, and that TBT may contribute to the amplification of Th2-predominance. We presume that lower basal levels of GSH in Th1 cells are important factors that determine the susceptibility of Th1 cells to TBT induced apoptosis. Based on the data we have presented here and previously, we propose a novel mechanism by which the environmental pollutants contribute to the increased prevalence of allergic diseases by induction of Th2 predominance via selective induction of apoptosis in differentiated Th1 cells as well as modulation of Th1/Th2 differentiation from naive CD4+ T cells.