Department of Analytical Chemistry, Medical University of Bialystok, 15-222 Bialystok, Poland.
LabOS, Rudjer Boskovic Institute, 10000 Zagreb, Croatia.
Int J Mol Sci. 2021 Sep 15;22(18):9956. doi: 10.3390/ijms22189956.
Although apoptosis of keratinocytes has been relatively well studied, there is a lack of information comparing potentially proapoptotic treatments for healthy and diseased skin cells. Psoriasis is a chronic autoimmune-mediated skin disease manifested by patches of hyperproliferative keratinocytes that do not undergo apoptosis. UVB phototherapy is commonly used to treat psoriasis, although this has undesirable side effects, and is often combined with anti-inflammatory compounds. The aim of this study was to analyze if cannabidiol (CBD), a phytocannabinoid that has anti-inflammatory and antioxidant properties, may modify the proapoptotic effects of UVB irradiation in vitro by influencing apoptotic signaling pathways in donor psoriatic and healthy human keratinocytes obtained from the skin of five volunteers in each group. While CBD alone did not have any major effects on keratinocytes, the UVB treatment activated the extrinsic apoptotic pathway, with enhanced caspase 8 expression in both healthy and psoriatic keratinocytes. However, endoplasmic reticulum (ER) stress, characterized by increased expression of caspase 2, was observed in psoriatic cells after UVB irradiation. Furthermore, decreased p-AKT expression combined with increased 15-d-PGJ level and p-p38 expression was observed in psoriatic keratinocytes, which may promote both apoptosis and necrosis. Application of CBD partially attenuated these effects of UVB irradiation both in healthy and psoriatic keratinocytes, reducing the levels of 15-d-PGJ, p-p38 and caspase 8 while increasing Bcl2 expression. However, CBD increased p-AKT only in UVB-treated healthy cells. Therefore, the reduction of apoptotic signaling pathways by CBD, observed mainly in healthy keratinocytes, suggests the need for further research into the possible beneficial effects of CBD.
尽管角质形成细胞的凋亡已经得到了相对较好的研究，但缺乏比较健康和患病皮肤细胞潜在促凋亡治疗的信息。银屑病是一种慢性自身免疫介导的皮肤病，表现为过度增殖的角质形成细胞不会发生凋亡的斑块。UVB 光疗常用于治疗银屑病，尽管它有不良的副作用，而且通常与抗炎化合物联合使用。本研究旨在分析大麻二酚（CBD）是否可以通过影响凋亡信号通路来改变 UVB 照射对体外供体银屑病和健康人角质形成细胞的促凋亡作用，CBD 是一种具有抗炎和抗氧化特性的植物大麻素。虽然 CBD 单独对角质形成细胞没有任何重大影响，但 UVB 处理激活了外在凋亡途径，在健康和银屑病角质形成细胞中增强了 caspase 8 的表达。然而，在 UVB 照射后，内质网（ER）应激，表现为 caspase 2 的表达增加，在银屑病细胞中观察到。此外，在银屑病角质形成细胞中观察到 p-AKT 表达减少，同时 15-d-PGJ 水平和 p-p38 表达增加，这可能促进凋亡和坏死。CBD 的应用部分减轻了健康和银屑病角质形成细胞中 UVB 照射的这些影响，降低了 15-d-PGJ、p-p38 和 caspase 8 的水平，同时增加了 Bcl2 的表达。然而，CBD 仅在 UVB 处理的健康细胞中增加了 p-AKT。因此，CBD 观察到的凋亡信号通路的减少，主要在健康角质形成细胞中，表明需要进一步研究 CBD 的可能有益作用。
