National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki 305-8506, Japan.
Toxicology. 2011 Aug 15;286(1-3):28-35. doi: 10.1016/j.tox.2011.05.002. Epub 2011 May 12.
To investigate the effect of low-level toluene inhalation on immune regulation in an allergic mouse model, C3H/HeN mice were exposed to 0, 5, 50, or 500ppm of toluene for 6h/day, 5 days/week for 3 or 6 weeks. For allergic mouse model, half of the mice in each group were immunized with ovalbumin (OVA). Allergic mice exposed to toluene for 3 weeks did not exhibit any changes in their plasma, lung or spleen samples. Although exposure to toluene alone for 6 weeks did not increase the number of inflammatory cells in bronchoalveolar lavage (BAL) fluid, coexposure to 50ppm toluene and OVA increased the number of BAL cells. Histological changes and increased amounts of fibronectin were observed in the lungs of OVA-immunized, 50-ppm-toluene-exposed mice. Exposure to 500ppm significantly increased the expressions of transcription factors STAT3, STAT4 and STAT5a mRNAs in spleen. In spleens from the allergic mouse model, the expressions of STAT3, STAT4, STAT5a, STAT6, GATA3 and Foxp3 mRNAs were significantly enhanced following exposure to 50ppm toluene for 6 weeks, but the expression of T-bet mRNA was not increased. Regarding the Th1/Th2 balance, the expressions of IL-4 and IL-12 mRNAs were enhanced in the spleens of toluene-exposed mice. Total IgG1 antibody production in the plasma was significantly increased in the 50-ppm-toluene-exposed allergic mouse model. These results indicate that low-level toluene exposure might dysregulate the allergic responses to OVA in C3H/HeN mice.
为了研究低浓度甲苯吸入对过敏性小鼠模型免疫调节的影响,将 C3H/HeN 小鼠暴露于 0、5、50 或 500ppm 甲苯中,每天 6 小时,每周 5 天,持续 3 或 6 周。对于过敏性小鼠模型,每组一半的小鼠用卵清蛋白(OVA)免疫。在甲苯暴露 3 周的过敏性小鼠的血浆、肺或脾样本中没有观察到任何变化。尽管单独暴露于甲苯 6 周不会增加支气管肺泡灌洗液(BAL)中炎症细胞的数量,但同时暴露于 50ppm 甲苯和 OVA 会增加 BAL 细胞的数量。OVA 免疫、50ppm 甲苯暴露的小鼠肺部观察到组织学变化和纤维连接蛋白含量增加。暴露于 500ppm 显著增加了脾脏中转录因子 STAT3、STAT4 和 STAT5a mRNA 的表达。在过敏性小鼠模型的脾脏中,暴露于 50ppm 甲苯 6 周后,STAT3、STAT4、STAT5a、STAT6、GATA3 和 Foxp3 mRNA 的表达显著增强,但 T-bet mRNA 的表达没有增加。关于 Th1/Th2 平衡,甲苯暴露小鼠脾脏中 IL-4 和 IL-12 mRNA 的表达增强。50ppm 甲苯暴露的过敏性小鼠模型血浆中总 IgG1 抗体的产生显著增加。这些结果表明,低浓度甲苯暴露可能会使 C3H/HeN 小鼠对 OVA 的过敏反应失调。