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三丁基锡(TBT)可增加 TNFα mRNA 的表达,并诱导体外鼠源巨噬细胞系凋亡。

Tributyltin (TBT) increases TNFα mRNA expression and induces apoptosis in the murine macrophage cell line in vitro.

机构信息

Fukushima Prefecture Ken-poku Public Health and Welfare Office, Fukushima, Japan.

出版信息

Environ Health Prev Med. 2004 Nov;9(6):266-71. doi: 10.1007/BF02898141.

Abstract

OBJECTIVE

Tributyltin (TBT) compounds have been widely used as antifouling agents for shipbottom paint. The immune system is a target of TBT intoxication. We evaluated the effects of TBT chloride in macrophages, which have critical roles in the immune system, using a murine macrophage lineage cell line, J774.1,in vitro.

METHODS

We examined tumor necrosis factor α (TNFα), interleukin-1β (IL-1β) andc-jun mRNA expression in J774.1 cells. The effects of TBT on the apoptosis of J774.1 cells were examined by determining the percentage of TUNEL-positive cells and caspase-3 activity.

RESULTS

The mean values of the viabilities of J774.1 cells exposed to TBT decreased dose-dependently. The relative mRNA expression of TNFα increased dose-dependently, however, that of IL-1β was not significantly different among the groups. The mean percentage of TUNEL-positive cells increased dose-dependently. Increases in the caspase-3 activities of J774.1 cells were observed in the groups exposed to higher concentrations of TBT. The mean value of relative mRNA expression of c-Jun transcription factor increased dose-dependently.

CONCLUSIONS

The increases in the percentage of TUNEL-positive cells and in caspase-3 activity suggested that exposure to TBT induces apoptosis of J774.1 cells. The increases in the mRNA expression of TNFα andc-jun by TBT may be related to apoptosis in macrophages.

摘要

目的

三丁基锡(TBT)化合物被广泛用作船底防污漆的防污剂。免疫系统是 TBT 中毒的靶标。我们使用体外鼠巨噬细胞系 J774.1 评估 TBT 氯化物对免疫系统中具有关键作用的巨噬细胞的影响。

方法

我们检测了 J774.1 细胞中肿瘤坏死因子-α(TNFα)、白细胞介素-1β(IL-1β)和 c-jun mRNA 的表达。通过测定 TUNEL 阳性细胞的百分比和 caspase-3 活性来检测 TBT 对 J774.1 细胞凋亡的影响。

结果

暴露于 TBT 的 J774.1 细胞的存活率呈剂量依赖性降低。TNFα 的相对 mRNA 表达呈剂量依赖性增加,而 IL-1β 在各组之间没有显著差异。TUNEL 阳性细胞的百分比呈剂量依赖性增加。在暴露于较高浓度 TBT 的组中观察到 J774.1 细胞中 caspase-3 活性的增加。c-Jun 转录因子的相对 mRNA 表达呈剂量依赖性增加。

结论

TUNEL 阳性细胞百分比和 caspase-3 活性的增加表明 TBT 暴露诱导 J774.1 细胞凋亡。TBT 引起的 TNFα 和 c-jun mRNA 表达的增加可能与巨噬细胞凋亡有关。

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