Acquired and innate immunity to polyaromatic hydrocarbons.
Acquired and innate immunity to polyaromatic hydrocarbons.
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DOI：
10.1016/j.taap.2006.12.009
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发表时间：
2007-11
影响因子：
3.8
通讯作者：
N. Yusuf;L. Timares;Megan D Seibert;Hui Xu;C. Elmets
中科院分区：
文献类型：
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作者：
N. Yusuf;L. Timares;Megan D Seibert;Hui Xu;C. Elmets
多芳烃是普遍存在的环境污染物，是强诱变剂和致癌物。研究人员利用这些特性来研究化学物质导致皮肤和其他器官癌症的机制。当应用于小鼠皮肤时，几种致癌的多芳香烃也被证明与免疫系统相互作用，刺激免疫反应并导致抗原特异性t细胞介导免疫的发展。细胞介导免疫的发展是菌株特异性的，由Ah受体基因和位于主要组织相容性复合体内的基因控制。CD8+T细胞是应答中的效应细胞，而CD4+T细胞则下调免疫。免疫反应的产生似乎具有保护作用，因为对致癌性多芳烃产生细胞介导免疫反应的小鼠品系在接受多芳烃皮肤致癌方案时，比没有产生免疫反应的小鼠更不可能产生肿瘤。在先天免疫方面，TLR4缺失的C3H/HeJ小鼠比TLR4正常的C3H/HeN小鼠更容易发生多芳氢皮肤肿瘤。这些发现支持了一种假设，即免疫反应通过与化学致癌物的相互作用，在预防化学皮肤癌的早期阶段发挥了积极作用。努力增强对引起肿瘤的化学物质的免疫反应可能是预防这些物质引起的肿瘤的有效方法。
Polyaromatic hydrocarbons are ubiquitous environmental pollutants that are potent mutagens and carcinogens. Researchers have taken advantage of these properties to investigate the mechanisms by which chemicals cause cancer of the skin and other organs. When applied to the skin of mice, several carcinogenic polyaromatic hydrocarbons have also been shown to interact with the immune system, stimulating immune responses and resulting in the development of antigen-specific T-cell-mediated immunity. Development of cell-mediated immunity is strain-specific and is governed by Ah receptor genes and by genes located within the major histocompatibility complex. CD8+T cells are effector cells in the response, whereas CD4+T cells down-regulate immunity. Development of an immune response appears to have a protective effect since strains of mice that develop a cell-mediated immune response to carcinogenic polyaromatic hydrocarbons are less likely to develop tumors when subjected to a polyaromatic hydrocarbon skin carcinogenesis protocol than mice that fail to develop an immune response. With respect to innate immunity, TLR4-deficient C3H/HeJ mice are more susceptible to polyaromatic hydrogen skin tumorigenesis than C3H/HeN mice in which TLR4 is normal. These findings support the hypothesis that immune responses, through their interactions with chemical carcinogens, play an active role in the prevention of chemical skin carcinogenesis during the earliest stages. Efforts to augment immune responses to the chemicals that cause tumors may be a productive approach to the prevention of tumors caused by these agents.