The adjuvant effect of di-(2-ethylhexyl) phthalate is mediated through a PPARα-independent mechanism
The adjuvant effect of di-(2-ethylhexyl) phthalate is mediated through a PPARα-independent mechanism
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DOI：
10.1016/j.toxlet.2007.03.009
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发表时间：
2007-05-15
影响因子：
3.5
通讯作者：
Nielsen, Gunnar Damgard
中科院分区：
文献类型：
--
作者：
Larsen, Soren Thor;Nielsen, Gunnar Damgard
先前在BALB/c小鼠中进行的研究显示，邻苯二甲酸二（2-乙基己基）酯（DEHP）对同时给予的卵清蛋白具有佐剂效应。DEHP是最常用的邻苯二甲酸酯增塑剂。DEHP在体内形成的代谢物是过氧化物酶体增殖物激活受体（PPAR）配体，这是一组可能具有免疫调节特性的化学物质。为了研究PPAR α受体是否参与DEHP的佐剂效应，将PPAR α缺陷型129/Sv小鼠腹腔内暴露于OVA和DEHP的混合物，并将OVA特异性IgE、IgG 1和IgG 2a反应与野生型菌株中的相应反应进行比较。该研究表明，DEHP的佐剂机制是通过不依赖于PPAR α的机制介导的。与仅给予OVA的小鼠相比，DEHP在野生型和PPARa敲除菌株中诱导了OVA特异性IgG 1和IgG 2a水平的高度增加，表明DEHP是一种混合的Th 1/Th 2佐剂。(C)2007年由Elsevier爱尔兰有限公司出版。
Previous studies in BALB/c mice revealed an adjuvant effect of di-(2-ethylhexyl) phthalate (DEHP) to simultaneously administered ovalbumin. DEHP is the most commonly used phthalate plasticizer. In vivo formed metabolites of DEHP are peroxisome-proliferator-activated receptor (PPAR) ligands, a group of chemicals that may have immunomodulatory properties. To study whether the PPAR alpha receptor was involved in the adjuvant effect of DEHP, PPAR alpha-deficient 129/Sv mice were exposed intraperitoneally to a mixture of OVA and DEHP, and the OVA-specific IgE, IgG1 and IgG2a responses were compared to the corresponding responses in the wild-type strain. The study showed that the adjuvant mechanism of DEHP is mediated through a PPAR alpha-independent mechanism. Compared to mice only given OVA, DEHP induced highly increased levels of OVA-specific IgG1 and IgG2a, both in the wild-type and in the PPARa knock-out strains, indicating that DEHP is a mixed Th1/Th2 adjuvant. (C) 2007 Published by Elsevier Ireland Ltd.