Yamamoto Shoji, Win-Shwe Tin-Tin, Yoshida Yasuhiro, Kunugita Naoki, Arashidani Keiichi, Fujimaki Hidekazu
National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan.
Inhal Toxicol. 2009 Aug;21(9):793-802. doi: 10.1080/08958370902798448.
The aim of the present study was to investigate the effect of low-level concentrations, under the occupational acceptable limits, of toluene exposure and peptidoglycan (PGN) stimulation on Th1/Th2 immunity in infant mice. Pregnant BALB/c mice and their offspring were exposed to low-level toluene inhalation (0, 5, and 50 ppm) for 4 wk (from the late prenatal stage to early postnatal stage) in a whole-body exposure chamber. Some of the pregnant mice and their offspring were stimulated with PGN during toluene exposure. We measured total immunoglobulins of different subclasses in plasma, and production and expression level of cytokines in the lung and spleen, and transcription factors related to Th1/Th2 immunity in the spleen of infant (3 wk old) mice. Exposure of mice to 5 or 50 ppm toluene resulted in increased immunoglobulin (Ig) G1 and decreased IgG2a and IgE antibodies in the plasma; significantly decreased T-bet, GATA-3, and Foxp3 mRNA in the spleen; and a tendency toward decreased interferon (IFN)-gamma mRNA in spleen. Exposure of mice to low-level toluene together with PGN stimulation resulted in decreased IgG1 as well as IgG2a antibodies in the plasma and Foxp3 mRNA in spleen as compared with control or PGN-treated mice. These findings suggest that low-level toluene exposure and PGN stimulation from the late prenatal to early postnatal stage suppressed the splenic parameter related to Th1/Th2 immunity in infant mice.
本研究的目的是调查职业可接受限度以下的低浓度甲苯暴露和肽聚糖(PGN)刺激对幼鼠Th1/Th2免疫的影响。将怀孕的BALB/c小鼠及其后代置于全身暴露舱中,暴露于低浓度甲苯吸入环境(0、5和50 ppm)4周(从产前后期到产后早期)。部分怀孕小鼠及其后代在甲苯暴露期间接受PGN刺激。我们检测了幼鼠(3周龄)血浆中不同亚类的总免疫球蛋白、肺和脾脏中细胞因子的产生和表达水平,以及脾脏中与Th1/Th2免疫相关的转录因子。小鼠暴露于5或50 ppm甲苯后,血浆中免疫球蛋白(Ig)G1增加,IgG2a和IgE抗体减少;脾脏中T-bet、GATA-3和Foxp3 mRNA显著降低;脾脏中干扰素(IFN)-γ mRNA有降低趋势。与对照或PGN处理的小鼠相比,小鼠在低浓度甲苯暴露并接受PGN刺激后,血浆中IgG1和IgG2a抗体以及脾脏中Foxp3 mRNA均降低。这些发现表明,从产前后期到产后早期的低浓度甲苯暴露和PGN刺激会抑制幼鼠脾脏中与Th1/Th2免疫相关的参数。