In vitro evaluation of the effects of perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) on IL-2 production in human T-cells.

In vitro evaluation of the effects of perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) on IL-2 production in human T-cells.
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DOI:
10.1002/jat.3037
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发表时间:
2015-05
影响因子:
3.3
通讯作者:
Kamen, Diane L.
Kamen, Diane L.
中科院分区:
医学4区
文献类型:
--
作者:
Midgett, Kristin;Peden-Adams, Margie M.;Gilkeson, Gary S.;Kamen, Diane L.

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全氟化合物,如全氟辛烷磺酸(PFOS)和全氟辛酸(PFOA),已被证明可以改变各种免疫功能,表明它们具有免疫毒性。本研究评估了全氟辛烷磺酸和全氟辛烷磺酸对人Jurkat T细胞系产生IL-2和健康人原代T细胞全氟辛烷磺酸的影响。分别用植物血凝素/佛波酯、抗CD-3/抗CD-2 8或抗CD-3刺激Jurkat细胞,并分别加入0、0.0 5、0.1、0.5、1、5、10、5、10、50、75或10 0μg m l−1全氟辛烷磺酸或0、0.005、0.0 1、0.0 1、0.1、0.5、1、5或10μg m l−1全氟辛酸。PHA/PMA或抗CD-3刺激的Jurkat细胞IL-2产生分别从50μg全氟辛烷磺酸毫升−-1和5μg全氟辛烷磺酸毫升−-1开始降低,而抗CD_3/抗CD-2 8刺激后与对照组相比无明显变化。将PPAR-α拮抗剂GW6471加入到PHA/PMA刺激的全氟辛烷磺酸刺激的细胞中,导致IL-2的产生从50μg全氟辛烷磺酸毫升−-1开始下降,这表明全氟辛烷磺酸通过PPAR-α非依赖机制影响T细胞IL-2的产生。Jurkat细胞暴露于全氟辛酸、全氟辛烷磺酸+GW6471或全氟辛烷磺酸+全氟辛酸时,IL-2的产生没有显著差异。使用健康的原代人类CD4+T细胞进行的体外剂量研究与Jurkat的结果一致。这些数据表明,全氟辛烷磺酸不影响IL-2的产生,但全氟辛烷磺酸在人类暴露范围的高端剂量水平上抑制了人类细胞系和人类原代细胞的IL-2产生。IL-2产生的减少是自身免疫性疾病的特征,如系统性红斑狼疮,应该进一步研究。
Perfluorinated compounds, such as perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), have been shown to alter various immune functions suggesting they are immunotoxic. This study assessed the effects of PFOS and PFOA on interleukin (IL)-2 production in the human Jurkat T-cell line and PFOS in healthy human primary T cells. Jurkat cells were stimulated with phytohemagglutinin (PHA)/phorbol myristate acetate (PMA), anti CD-3/anti CD-28, or anti CD-3, and dosed with 0, 0.05, 0.1, 0.5, 1, 5, 10, 50, 75, or 100 μg ml−1 PFOS or 0, 0.005, 0.01, 0.05, 0.1, 0.5, 1, 5, or 10 μg ml−1 PFOA. Jurkat cells stimulated with PHA/PMA or anti CD-3 exhibited decreased IL-2 production beginning at 50 μg PFOS ml−1 and 5 μg PFOS ml−1 respectively, but stimulation with anti-CD3/anti-CD28 resulted in no changes compared with the control. Addition of the PPAR-alpha antagonist GW6471 to PFOS-dosed cells stimulated with PHA/PMA resulted in decreases in IL-2 production starting at 50 μg PFOS ml−1, which suggests PFOS affected T-cell IL-2 production via PPAR-alpha-independent mechanisms. Exposure to PFOA, PFOA + GW6471, or PFOS + PFOA in Jurkat cells resulted in no significant differences in IL-2 production. In vitro dosing studies using healthy primary human CD4+ T cells were consistent with the Jurkat results. These data demonstrated that PFOA did not impact IL-2 production, but PFOS suppressed IL-2 production in both a human cell line and human primary cells at dose levels within the high end of the human exposure range. A decrease in IL-2 production is characteristic of autoimmune diseases such as systemic lupus erythematosus and should be further investigated.
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发表时间: 2012-02-01
影响因子: 1.5
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期刊: CYTOMETRY
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