Guo T L, Zhang X L, Leffel E K, Peachee V L, Karrow N A, Germolec D R, White K L
Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298-0613, USA.
J Appl Toxicol. 2002 Nov-Dec;22(6):397-403. doi: 10.1002/jat.876.
It has been reported that dermal exposure to trimellitic anhydride (TMA, 50%), a respiratory allergen, induced greater production of serum IgE and expression of Th2 cytokines than 2,4-dinitrochlorobenzene (DNCB, 1%), a potent contact sensitizer, in female BALB/C mice. To determine if there is any strain difference, four strains (B6C3F1, C57BL/6, BDF1 and BALB/C) of female mice were employed in this study to compare the differential effects of these chemicals on the hypersensitivity responses. Serum IgE levels were increased in TMA-treated B6C3F1, C57BL/6 and BDF1 mice when compared with the DNCB treatment and vehicle controls; in contrast, no difference was observed between TMA- and DNCB-treated BALB/C mice, although both chemicals induced greater IgE production than vehicle controls. In vitro expression of interleukin 4 (IL-4) and IL-13 mRNA by overnight concanavalin A (ConA)-stimulated draining lymph node cells was enhanced following in vivo treatment with TMA but not with DNCB in the B6C3F1, C57BL/6 and BDF1 mice. In contrast, TMA and DNCB induced similar levels of IL-4 and IL-13 mRNA in the BALB/C mice. The IL-4 protein levels in the supernatants of overnight ConA-treated draining lymph node cells were also increased in TMA-treated B6C3F1 and C57BL/6 mice when compared with the DNCB treatment and vehicle controls. Further mechanistic evaluation in the B6C3F1 mice indicated that the activation of STAT6 but not STAT4 by ConA plus IL-2-treated draining lymph node cells was increased in TMA- but not DNCB-treated mice when compared with the vehicle controls. Furthermore, surface expression of B7.2 (CD86) by B cells was increased in both TMA- and DNCB-treated B6C3F1 mice when compared with the vehicles; however, greater B7.2 expression was observed in TMA-treated compared with DNCB-treated. Overall, these results demonstrate that a similar pattern of IgE and cytokine production was observed in these strains of mice except for BALB/C. Furthermore, differential activation of STAT6 and expression of CD86 following exposure to TMA and DNCB may contribute to the differential production of IgE and cytokines.
据报道，在雌性BALB/C小鼠中，皮肤接触呼吸道过敏原偏苯三酸酐（TMA，50%）比强效接触致敏剂2,4-二硝基氯苯（DNCB，1%）诱导产生更高水平的血清IgE和Th2细胞因子表达。为了确定是否存在品系差异，本研究使用了四种品系（B6C3F1、C57BL/6、BDF1和BALB/C）的雌性小鼠来比较这些化学物质对超敏反应的不同影响。与DNCB处理组和溶剂对照组相比，TMA处理的B6C3F1、C57BL/6和BDF1小鼠的血清IgE水平升高；相反，TMA处理组和DNCB处理组的BALB/C小鼠之间未观察到差异，尽管两种化学物质诱导产生的IgE均高于溶剂对照组。在B6C3F1、C57BL/6和BDF1小鼠中，体内经TMA处理而非DNCB处理后，伴刀豆球蛋白A（ConA）过夜刺激的引流淋巴结细胞中白细胞介素4（IL-4）和IL-13 mRNA的体外表达增强。相比之下，TMA和DNCB在BALB/C小鼠中诱导产生相似水平的IL-4和IL-13 mRNA。与DNCB处理组和溶剂对照组相比，TMA处理的B6C3F1和C57BL/6小鼠中，ConA过夜处理的引流淋巴结细胞上清液中的IL-4蛋白水平也升高。在B6C3F1小鼠中进行的进一步机制评估表明，与溶剂对照组相比，ConA加IL-2处理的引流淋巴结细胞对STAT6而非STAT4的激活在TMA处理组小鼠中增加，而在DNCB处理组小鼠中未增加。此外，与溶剂组相比，TMA和DNCB处理的B6C3F1小鼠中B细胞表面B-7.2（CD86）的表达均增加；然而，与DNCB处理组相比，TMA处理组中观察到更高的B-7.2表达。总体而言，这些结果表明，除BALB/C外，在这些品系的小鼠中观察到了相似的IgE和细胞因子产生模式。此外，暴露于TMA和DNCB后STAT6的不同激活和CD86的表达可能导致IgE和细胞因子的不同产生。
