大麻素系统和细胞因子网络。

T. Klein, B. Lane, C. Newton, H. Friedman
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引用次数: 142

摘要

在过去的几年里,关于我们对构成大麻素系统的受体和配体的理解取得了许多进展。同样,围绕细胞因子生物学的科学也取得了进步,使我们能够更精确地测量这些蛋白质,并理解和解释它们水平变化的意义。科学家们希望研究吸食大麻对健康的影响,并了解内源性大麻拟配体在免疫调节中的可能作用,他们继续研究这些物质对细胞因子网络的调节和发育的影响。研究表明,存在两种主要的大麻素受体亚型,其中亚型1 (CB1)主要在大脑中表达,而亚型2 (CB2)主要在外周表达。各种基于大麻素结构的受体配体以及低亲和化合物、非大麻素配体和由脂肪酸类二十烷衍生的内源性配体已经被合成和研究。高选择性受体拮抗剂也被引入和研究。人工合成的低亲和力配体如(+)-HU-211和DMH-11C已被证明可能通过抑制tnf - α和其他急性期细胞因子的产生和作用而具有抗炎作用。此外,暴露于高亲和力和精神活性配体(如大麻和四氢大麻酚)后,TNF和其他细胞因子如GM-CSF、IL-6、IFNgamma和IL-12也被发现受到抑制。然而,其中一些配体也显示出增加而不是减少白细胞介素如IL-1、IL-4、IL-10和IL-6,细胞因子如tnf - α和趋化因子如IL-8、MIP-1和RANTES。内源性配体anandamide已经在培养中被证明可以抑制催乳素的增殖反应或增强对IL-3和IL-6等细胞因子的反应。这种类二十烷也被证明可以增加白细胞介素和其他细胞因子的产生。大麻素受体已被证明参与了这些影响的一部分,但不是全部。很明显,精神活性和非精神活性化合物已经在体内和体外证明了对多种细胞因子的产生和功能的影响。根据模型系统的不同,这些影响往往是相互冲突的,大麻素受体的参与尚不清楚。然而,有足够的证据表明大麻素系统显著影响细胞因子网络的功能,这种关联可能为某些免疫疾病的机制提供线索,并形成新的免疫疗法的基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The cannabinoid system and cytokine network.
Many advances have been made in the last few years concerning our understanding of the receptors and ligands composing the cannabinoid system. Likewise, the science surrounding cytokine biology has advanced enabling us to measure these proteins more precisely as well as understand and interpret the meaning of changes in their levels. Scientists wishing to study the health consequences of smoking marijuana as well as understand the possible role of endogenous cannabimimetic ligands in immune regulation have continued to study the influence of these substances on the regulation and development of the cytokine network. Research has shown that two major cannabinoid receptor subtypes exist and that subtype 1 (CB1) is expressed primarily in the brain whereas subtype 2 (CB2) is expressed primarily in the periphery. A variety of ligands for these receptors based on the cannabinoid structure have been synthesized and studied as well as low affinity compounds, noncannabinoid ligands, and endogenous ligands derived from fatty acid eicosanoids. Highly selective receptor antagonists have also been introduced and studied. Synthetic, low affinity ligands such as (+)-HU-211 and DMH-11C have been shown to cause anti-inflammatory effects possibly through inhibiting the production and action of TNF-alpha and other acute phase cytokines. In addition, suppression of TNF and other cytokines such as GM-CSF, IL-6, IFNgamma, and IL-12 has also been seen following exposure to high affinity and psychoactive ligands such as marijuana and THC. However, some of these ligands have also been shown to increase rather than decrease interleukins such as IL-1, IL-4, IL-10, and IL-6, cytokines such as TNF-alpha, and chemokines such as IL-8, MIP-1, and RANTES. The endogenous ligand, anandamide, has been shown in culture to either suppress the proliferation response to prolactin or enhance the response to cytokines such as IL-3 and IL-6. This eicosanoid has also been shown to increase the production of interleukins and other cytokines. Cannabinoid receptors have been shown to be involved in some but not all of these effects. It is clear that psychoactive and nonpsychoactive compounds have demonstrated effects in vivo and in vitro on the production and function of a variety of cytokines. Depending upon the model system, these effects are often conflicting, and the involvement of cannabinoid receptors is unclear. However, enough evidence exists to suggest that the cannabinoid system significantly impacts the functioning of the cytokine network, and this association may provide clues to the mechanisms of certain immune diseases and form the basis for new immunotherapies.
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