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产前暴露于大麻素后免疫改变的表观遗传调控及其对后代的长期影响。

Epigenetic Regulation of Immunological Alterations Following Prenatal Exposure to Marijuana Cannabinoids and its Long Term Consequences in Offspring.

作者信息

Zumbrun Elizabeth E, Sido Jessica M, Nagarkatti Prakash S, Nagarkatti Mitzi

机构信息

Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, 6439 Garners Ferry Road, Columbia, SC, 29208, USA.

出版信息

J Neuroimmune Pharmacol. 2015 Jun;10(2):245-54. doi: 10.1007/s11481-015-9586-0. Epub 2015 Jan 25.

Abstract

Use of marijuana during pregnancy is fairly commonplace and can be expected increase in frequency as more states legalize its recreational use. The cannabinoids present in marijuana have been shown to be immunosuppressive, yet the effect of prenatal exposure to cannabinoids on the immune system of the developing fetus, its long term consequences during adult stage of life, and transgenerational effects have not been well characterized. Confounding factors such as co-existing drug use make the impact of cannabis use on progeny inherently difficult to study in a human population. Data from various animal models suggests that in utero exposure to cannabinoids results in profound T cell dysfunction and a greatly reduced immune response to viral antigens. Furthermore, evidence from animal studies indicates that the immunosuppressive effects of cannabinoids can be mediated through epigenetic mechanisms such as altered microRNA, DNA methylation and histone modification profiles. Such studies support the hypothesis that that parental or prenatal exposure to cannabis can trigger epigenetic changes that could have significant immunological consequences for offspring as well as long term transgenerational effects.

摘要

孕期使用大麻相当普遍,随着越来越多的州将其娱乐性使用合法化,预计其使用频率还会增加。大麻中含有的大麻素已被证明具有免疫抑制作用,但产前接触大麻素对发育中胎儿免疫系统的影响、其在成年期的长期后果以及跨代效应尚未得到充分描述。诸如同时使用其他药物等混杂因素使得在人群中研究大麻使用对后代的影响本质上变得困难。来自各种动物模型的数据表明,子宫内接触大麻素会导致严重的T细胞功能障碍,并大大降低对病毒抗原的免疫反应。此外,动物研究的证据表明,大麻素的免疫抑制作用可通过表观遗传机制介导,如微小RNA改变、DNA甲基化和组蛋白修饰谱改变。此类研究支持这样的假设,即父母或产前接触大麻会引发表观遗传变化,这可能对后代产生重大免疫后果以及长期的跨代效应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d418/4470789/c1df8cf8cd0d/nihms678993f1.jpg

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