Department of Pharmacology, School of Pharmacy, University of Granada, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Granada, Spain.
Br J Pharmacol. 2010 Aug;160(7):1714-26. doi: 10.1111/j.1476-5381.2010.00827.x.
Cyclooxygenase 2 (COX-2) is involved in inflammatory bowel disease, but the effect of flavonoids at the intestinal epithelial level is unknown. We aimed to characterize the effect and structure-activity relationship of nine selected flavonoids on COX-2 expression in intestinal epithelial cell (IEC)18 cells. We also investigated the signal transduction pathway(s) responsible for the effects observed.
Intestinal epithelial cell 18, a non-tumour cell line with intestinal epithelial phenotype, was used. COX-2 was measured by Western blot and the involvement of the NF-kappaB pathway assessed by Western blot, pharmacological inhibition, luciferase reporter assays and nuclear translocation experiments.
The effect of flavonoids on COX-2 expression depended on the experimental conditions tested [non-stimulated and lipopolysaccharide (LPS)-stimulated]. Flavonoids caused an increase in COX-2 expression and NF-kappaB-dependent gene transcription under basal conditions. Conversely, under LPS stimulation flavonoids increased, decreased or did not affect COX-2 levels depending on the specific type. Variable effects were observed on extracellular signal regulated kinase/p38/c-Jun N-terminal kinase phosphorylation and p50/65 nuclear translocation.
The effect of flavonoids on COX-2 expression depended on the balance of the interference with IkappaB-alpha phosphorylation and other signalling targets, and therefore depends on the experimental conditions and on the type of flavonoids. This is expected to result in different effects in inflammatory conditions. In general, flavonoids may limit epithelial COX-2 expression in inflammatory conditions while favouring it when inflammation is not present.
环氧化酶 2（COX-2）参与了炎症性肠病，但黄酮类化合物在肠道上皮细胞水平的作用尚不清楚。我们旨在描述 9 种选定的黄酮类化合物对 IEC18 细胞中 COX-2 表达的影响及其构效关系。我们还研究了负责观察到的影响的信号转导途径。
使用具有肠上皮表型的非肿瘤细胞系 IEC18 细胞。通过 Western blot 测定 COX-2，通过 Western blot、药理学抑制、荧光素酶报告基因测定和核转位实验评估 NF-κB 途径的参与情况。
黄酮类化合物对 COX-2 表达的影响取决于所测试的实验条件[非刺激和脂多糖（LPS）刺激]。在基础条件下，黄酮类化合物会导致 COX-2 表达增加和 NF-κB 依赖性基因转录。相反，在 LPS 刺激下，黄酮类化合物会根据具体类型增加、减少或不影响 COX-2 水平。细胞外信号调节激酶/p38/c-Jun N-末端激酶磷酸化和 p50/65 核转位的变化。
黄酮类化合物对 COX-2 表达的影响取决于对 IkappaB-α磷酸化和其他信号靶点的干扰的平衡，因此取决于实验条件和黄酮类化合物的类型。这预计会在炎症条件下产生不同的影响。一般来说，在炎症情况下，黄酮类化合物可能会限制上皮细胞 COX-2 的表达，而在没有炎症的情况下则有利于其表达。
