Department of Analytical Chemistry, Medical University of Bialystok, 15-089 Białystok, Poland.
Department of Histology and Cytophysiology, Medical University of Bialystok, 15-089 Białystok, Poland.
Biomolecules. 2022 Jun 17;12(6):842. doi: 10.3390/biom12060842.
Inflammation and apoptosis are regulated by similar factors, including ultraviolet B (UVB) radiation and cannabinoids, which are metabolized by cyclooxygenase-2 (COX-2) into pro-apoptotic prostaglandin derivatives. Thus, the aim of this study was to evaluate the impact of cyclooxygenase-2 inhibition by celecoxib on the apoptosis of keratinocytes modulated by UVB, anandamide (AEA) and cannabidiol (CBD). For this purpose, keratinocytes were non-treated/treated with celecoxib and/or with UVB and CBD and AEA. Apoptosis was evaluated using microscopy, gene expressions using quantitate reverse-transcriptase polymerase chain reaction; prostaglandins using liquid chromatography tandem mass spectrometry and cyclooxygenase activity using spectrophotometry. UVB enhances the percentage of apoptotic keratinocytes, which can be caused by the increased prostaglandin generation by cyclooxygenase-2, or/and induced cannabinoid receptor 1/2 (CB1/2) expression. AEA used alone intensifies apoptosis by affecting caspase expression, and in UVB-irradiated keratinocytes, cyclooxygenase-2 activity is increased, while CBD acts as a cytoprotective when used with or without UVB. After COX-2 inhibition, UVB-induced changes are partially ameliorated, when anandamide becomes an anti-apoptotic agent. It can be caused by observed reduced generation of anandamide pro-apoptotic derivative prostaglandin-ethanolamide by COX. Therefore, products of cyclooxygenase-dependent lipid metabolism seem to play an important role in the modulation of UVB-induced apoptosis by cannabinoids, which is particularly significant in case of AEA as inhibition of cyclooxygenase reduces the generation of pro-apoptotic lipid mediators and thus prevents apoptosis.
炎症和细胞凋亡受相似因素调控，包括紫外线 B（UVB）辐射和大麻素，后者经环氧化酶-2（COX-2）代谢为促凋亡的前列腺素衍生物。因此，本研究旨在评估塞来昔布对 COX-2 抑制对 UVB、大麻素（AEA）和大麻二酚（CBD）调节的角质形成细胞凋亡的影响。为此，角质形成细胞未经处理/用塞来昔布和/或用 UVB 和 CBD 及 AEA 处理。使用显微镜评估细胞凋亡，使用定量逆转录聚合酶链反应评估基因表达；使用液相色谱串联质谱法评估前列腺素，使用分光光度法评估环氧化酶活性。UVB 增加了凋亡角质形成细胞的百分比，这可能是 COX-2 产生的前列腺素增加所致，或者/和诱导大麻素受体 1/2（CB1/2）表达所致。AEA 单独使用会通过影响半胱天冬酶表达来增强凋亡，而在 UVB 照射的角质形成细胞中，COX-2 活性增加，而 CBD 在与或不与 UVB 一起使用时作为细胞保护剂。COX-2 抑制后，AEA 成为一种抗凋亡剂，UVB 诱导的变化部分得到改善。这可能是由于 COX 观察到的 AEA 促凋亡衍生物前列腺素乙醇胺生成减少所致。因此，环氧化酶依赖性脂质代谢产物似乎在大麻素调节 UVB 诱导的细胞凋亡中发挥重要作用，在 AEA 的情况下尤其重要，因为 COX 抑制减少了促凋亡脂质介质的生成，从而防止了细胞凋亡。
