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首页> 外文期刊>Journal of dermatological science >Cannabinoids inhibit human keratinocyte proliferation through a non-CB1/CB2 mechanism and have a potential therapeutic value in the treatment of psoriasis.
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Cannabinoids inhibit human keratinocyte proliferation through a non-CB1/CB2 mechanism and have a potential therapeutic value in the treatment of psoriasis.

机译:大麻素通过非CB1 / CB2机制抑制人角质形成细胞的增殖,在牛皮癣的治疗中具有潜在的治疗价值。

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BACKGROUND: Cannabinoids from cannabis (Cannabis sativa) are anti-inflammatory and have inhibitory effects on the proliferation of a number of tumorigenic cell lines, some of which are mediated via cannabinoid receptors. Cannabinoid (CB) receptors are present in human skin and anandamide, an endogenous CB receptor ligand, inhibits epidermal keratinocyte differentiation. Psoriasis is an inflammatory disease also characterised in part by epidermal keratinocyte hyper-proliferation. OBJECTIVE: We investigated the plant cannabinoids Delta-9 tetrahydrocannabinol, cannabidiol, cannabinol and cannabigerol for their ability to inhibit the proliferation of a hyper-proliferating human keratinocyte cell line and for any involvement of cannabinoid receptors. METHODS: A keratinocyte proliferation assay was used to assess the effect of treatment with cannabinoids. Cell integrity and metabolic competence confirmed using lactate-dehydrogenase and adenosine tri-phosphate assays. To determine the involvement of the receptors, specific agonist and antagonist were used in conjunction with some phytocannabinoids. Western blot and RT-PCR analysis confirmed presence of CB1 and CB2 receptors. RESULTS: The cannabinoids tested all inhibited keratinocyte proliferation in a concentration-dependent manner. The selective CB2 receptor agonists JWH015 and BML190 elicited only partial inhibition, the non-selective CB agonist HU210 produced a concentration-dependent response, the activity of theses agonists were not blocked by either CB1/CB2 antagonists. CONCLUSION: The results indicate that while CB receptors may have a circumstantial role in keratinocyte proliferation, they do not contribute significantly to this process. Our results show that cannabinoids inhibit keratinocyte proliferation, and therefore support a potential role for cannabinoids in the treatment of psoriasis.
机译:背景:来自大麻(大麻)的大麻素具有抗炎作用,并且对许多致瘤细胞系的增殖具有抑制作用,其中一些是通过大麻素受体介导的。人体皮肤中存在大麻素(CB)受体,内源性CB受体配体anandamide抑制表皮角质形成细胞分化。牛皮癣是一种炎症性疾病,其特征还在于表皮角质形成细胞过度增殖。目的:我们研究了植物大麻素Delta-9四氢大麻酚,大麻二酚,大麻酚和大麻二酚抑制过度增殖的人类角质形成细胞系增殖的能力以及大麻素受体的任何参与。方法:使用角质形成细胞增殖测定法评估大麻素治疗的效果。使用乳酸脱氢酶和三磷酸腺苷测定证实了细胞完整性和代谢能力。为了确定受体的参与,将特定的激动剂和拮抗剂与一些植物大麻素一起使用。蛋白质印迹和RT-PCR分析证实存在CB1和CB2受体。结果:测试的大麻素均以浓度依赖性方式抑制了角质形成细胞的增殖。选择性CB2受体激动剂JWH015和BML190仅引起部分抑制,非选择性CB激动剂HU210产生浓度依赖性反应,这些激动剂的活性均不受任何一种CB1 / CB2拮抗剂的阻断。结论:结果表明,尽管CB受体可能在角质形成细胞增殖中具有间接作用,但它们对这一过程没有显着贡献。我们的结果表明,大麻素抑制角质形成细胞的增殖,因此支持大麻素在银屑病治疗中的潜在作用。

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