Children's Immunology, what can we learn from animal studies (2): Modulation of systemic Th1/Th2 immune response in infant mice after prenatal exposure to low-level toluene and toll-like receptor (TLR) 2 ligand
Children's Immunology, what can we learn from animal studies (2): Modulation of systemic Th1/Th2 immune response in infant mice after prenatal exposure to low-level toluene and toll-like receptor (TLR) 2 ligand
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DOI：
10.2131/jts.34.sp341
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发表时间：
2009-07-01
影响因子：
2
通讯作者：
Fujimaki, Hidekazu
中科院分区：
文献类型：
--
作者：
Yamamoto, Shoji;Tin-Tin-Win-Shwe;Fujimaki, Hidekazu
据报道，新生儿免疫系统在数量和功能上与成人不同。免疫系统的发育对儿童疾病具有重要意义。出生前或哺乳期免疫系统的不成熟可能导致对环境有毒化学品暴露的敏感性。在本研究中，为了阐明在发育阶段低水平甲苯暴露油免疫功能的影响，妊娠小鼠从妊娠第14天至第19天暴露于0、5和50 ppm甲苯，有或没有革兰氏阳性细菌细胞壁组分（Toll样受体（TLR）2配体）的肽聚糖（PGN）刺激。采用ELISA和实时荧光定量RT-PCR方法检测3周龄时子代Th 1/Th 2平衡。小鼠暴露于50 ppm甲苯可增强血浆中总免疫球蛋白（IG）G2 a（Th 1依赖性）水平。另一方面，在这些小鼠中，转录因子T-bet（Th 1特异性）、加塔-3（Th 2特异性）和Foxp 3（调节性CD 4 + CD 25 + T细胞的基因标记物）mRNA的脾脏表达被抑制，但在5或50 ppm甲苯与PGN的组合中不被抑制。此外，在5或50 ppm甲苯与PGN的组合中，总IgG 1（Th 2依赖性）水平受到抑制。我们的研究结果表明，调制的Th 1和Th 2的反应可能会发生在低水平的甲苯暴露和/或结合PGN刺激的幼鼠。
It has been reported that the newborn immune system differs quantitatively and functionally from that of adults. Development of the immune system has important implications for childhood diseases. The immaturity of the immune system in the prenatal or Suckling stage may contribute to susceptibility to environmental toxic chemical exposure. In the present Study, to clarify the effect of low-level toluene exposure oil immune functions during developmental stage, pregnant mice were exposed to 0, 5, and 50 ppm toluene from gestational day 14 to day 19 with or without stimulation by peptidoglycan (PGN) of a Gram-positive bacterial cell wall component, a toll-like receptor (TLR) 2 ligand. We examined Th1/Th2 balance in the offspring's at 3 weeks old using ELISA and real-time RT-PCR methods. Exposure of mice to 50 ppm toluene enhanced total immunoglobulin (Ig) G2a (Th1-dependent) level in plasma. Oil the other hand, splenic expression of transcription factor T-bet (Th1-specific), GATA-3 (Th2-specific) and Foxp3 (gene marker for regulatory CD4+CD25+ T-cells) mRNAs Was Suppressed In these mice, but not in the combination of 5 or 50 ppm toluene with PGN. In addition, total IgG1 (Th2 dependent) level was Suppressed in the combination of 5 or 50 ppm toluene with PGN. Our findings indicate that modulation of Th1- and Th2-responses may occur in low-level toluene exposure and/or combination with PGN stimulation in infant mice.