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Differential stimulation of IgE production, STAT activation and cytokine and CD86 expression by 2,4-dinitrochlorobenzene and trimellitic anhydride

Guo TL, Zhang XL, Leffel EK, Peachee VL, Karrow NA, Germolec DR, White KL Jr.
Journal of Immunotoxicology (2018) DOI: https://doi.org/10.1002/jat.876 PMID: 12424743



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.