Subchronic effects of perfluorooctanesulfonate exposure on inflammation in adult male C57BL/6 mice
Subchronic effects of perfluorooctanesulfonate exposure on inflammation in adult male C57BL/6 mice
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DOI：
10.1002/tox.20642
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发表时间：
2012-05-01
影响因子：
4.5
通讯作者：
He, Qin-Cheng
中科院分区：
文献类型：
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作者：
Dong, Guang-Hui;Zhang, Ying-Hua;He, Qin-Cheng
以往的研究表明，暴露于全氟辛烷磺酸（PFOS），一种普遍存在的和高度持久性的环境污染物，诱导小鼠的免疫毒性。然而，很少有研究专门评估全氟辛烷磺酸对炎症的影响。该研究采用了标准的60天口服接触期，以评估全氟辛烷磺酸对炎症细胞因子[肿瘤坏死因子-a、白细胞介素-1 β和白细胞介素-6]反应的影响。成年雄性C57 BL/6小鼠每天经口灌胃给予0、0.0083、0.0167、0.0833、0.4167、0.8333或2.0833毫克/千克/天的全氟辛烷磺酸，从而在60天内分别获得0、0.5、1、5、25、50或125毫克全氟辛烷磺酸/千克的目标总给药剂量。全氟辛烷磺酸浓度为1毫克/千克时，腹腔巨噬细胞（CD 11b+细胞）的百分比以剂量依赖方式显著增加。当全氟辛烷磺酸浓度达到5毫克/千克/升时，腹腔巨噬细胞的体外IL-1 β产生量大幅增加。此外，全氟辛烷磺酸暴露显著增强了腹腔和脾脏巨噬细胞在体外或体内受到脂多糖刺激时产生的TNF-α、IL-1 β和IL-6。在体内LPS刺激下观察到的这些炎性细胞因子的血清水平因接触全氟辛烷磺酸而大幅升高。接触全氟辛烷磺酸会增加脾脏中促炎细胞因子TNF-α、IL-1 β、IL-6和原癌基因c-myc的表达。这些数据表明，接触全氟辛烷磺酸会调节炎症反应，需要进一步研究以确定其作用机制。(C)2010 Wiley Periodicals，Inc.环境毒理学，2012年。
Previous studies indicate that exposure to perfluorooctanesulfonate (PFOS), a ubiquitous and highly persistent environmental contaminant, induces immunotoxicity in mice. However, few studies have specifically assessed the effects of PFOS on inflammation. This study utilized a standard 60-day oral exposure period to assess the effects of PFOS on the response of inflammatory cytokines [tumor necrosis factor a (TNF-a), interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6)]. Adult male C57BL/6 mice were dosed daily by oral gavage with PFOS at 0, 0.0083, 0.0167, 0.0833, 0.4167, 0.8333 or 2.0833 mg/kg/day to yield a targeted Total Administered Dose (TAD) over 60 days of 0, 0.5, 1, 5, 25, 50, or 125 mg PFOS/kg, respectively. The percentage of peritoneal macrophages (CD11b+ cells) was significantly increased at concentrations =1 mg PFOS/kg TAD in a dose-dependent manner. Ex vivo IL-1 beta production by peritoneal macrophages was elevated substantially at concentrations of =5 mg PFOS/kg TAD. Moreover, PFOS exposure markedly enhanced the ex vivo production of TNF-a, IL-1 beta and IL-6 by peritoneal and splenic macrophages when stimulated either in vitro or in vivo with lipopolysaccharide (LPS). The serum levels of these inflammatory cytokines observed in response to in vivo stimulation with LPS were elevated substantially by exposure to PFOS. PFOS exposure elevated the expression of pro-inflammatory cytokines TNF-a, IL-1 beta, IL-6, and proto-oncogene, c-myc, in the spleen. These data suggest that exposure to PFOS modulates the inflammatory response, and further research is needed to determine the mechanism of action. (C) 2010 Wiley Periodicals, Inc. Environ Toxicol, 2012.