Chronic exposure to a trichloroethylene metabolite in autoimmune-prone MRL+/+ mice promotes immune modulation and alopecia
Chronic exposure to a trichloroethylene metabolite in autoimmune-prone MRL+/+ mice promotes immune modulation and alopecia
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DOI：
10.1093/toxsci/kfl149
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发表时间：
2007-02-01
影响因子：
3.8
通讯作者：
Gilbert, Kathleen M.
中科院分区：
文献类型：
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作者：
Blossom, Sarah J.;Doss, Jason C.;Gilbert, Kathleen M.
工业溶剂三氯乙烯（TCE）是一种广泛存在的环境污染物，已知会影响免疫系统。在本研究中，雌性MRL+/+小鼠在饮用水中接受三氯乙醛水合物（TCAH）（TCE的代谢产物）治疗40周。将结果与早期研究的数据进行比较，在该研究中，MRL+/+小鼠暴露于TCAH 4周。经过40周的暴露，小鼠出现皮肤炎症和剂量依赖性脱发。此外，TCAH似乎通过促进活化/效应子（即，CD 62 L（lo））表型，分泌促炎细胞因子干扰素-γ的能力增加。然而，与仅暴露4周后观察到的情况不同，TCAH并未显著减弱活化诱导细胞死亡（AICD）或CD 4（+）T细胞中死亡受体FasL的表达。一些金属蛋白酶（MMPs）被认为通过诱导FasL脱落在AICD的易感性中起作用。因此，检测了4周和40周血清的MMP-7水平，试图解释TCAH对AICD和FasL表达的不同结果。暴露于TCAH 4周的小鼠血清MMP-7水平显著升高。与此相反，血清MMP-7水平增加，在所有的小鼠40周相比，非自身免疫性菌株。总之，长期暴露于TCAH会促进脱发和皮肤炎症。TCAH对MMP-7水平的早期影响可能提供了TCAH促进皮肤病理学的机制。
The industrial solvent trichloroethylene (TCE) is a widespread environmental contaminant known to impact the immune system. In the present study, female MRL+/+ mice were treated for 40 weeks with trichloroacetaidehyde hydrate (TCAH), a metabolite of TCE, in the drinking water. The results were compared with the data from an earlier study in which MRL+/+ mice were exposed to TCAH for 4 weeks. Following a 40-week exposure, the mice developed skin inflammation and dose-dependent alopecia. In addition, TCAH appeared to modulate the CD4(+) T-cell subset by promoting the expression of an activated/effector (i.e., CD62L(lo)) phenotype with an increased capacity to secrete the proinflammatory cytokine interferon-gamma. However, unlike what was observed after only 4 weeks of exposure, TCAH did not significantly attenuate activation-induced cell death (AICD) or the expression of the death receptor FasL in CD4(+) T cells. Some metalloproteinases (MMPs) are thought to play a role in susceptibility to AICD by inducing FasL shedding. Thus, both the 4- and 40-week sera were tested for MMP-7 levels in an attempt to explain the disparate results of TCAH on AICD and FasL expression. Serum MMP-7 levels were significantly higher in mice exposed to TCAH for 4 weeks. In contrast, the serum MMP-7 levels were increased in all the mice by 40 weeks when compared with a nonautoimmune strain. Taken together, a chronic exposure to TCAH promotes alopecia and skin inflammation. The early effects of TCAH on MMP-7 levels may provide a mechanism by which TCAH promotes skin pathology.