NF-κB activation in renal tubular epithelial cells by oxalate stimulation
NF-κB activation in renal tubular epithelial cells by oxalate stimulation
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DOI：
10.1111/j.1442-2042.2008.02131.x
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发表时间：
2008-10-01
影响因子：
2.6
通讯作者：
Kohri, Kenjiro
中科院分区：
文献类型：
--
作者：
Tozawa, Keiichi;Yasui, Takahiro;Kohri, Kenjiro
目的：转录因子核因子-kappaB通过诱导多种细胞因子和生长因子参与炎症和免疫反应。近年来，骨桥蛋白(OPN)的表达与核因子-kappaB和激活蛋白-1的协同作用被报道。在本研究中，我们证明了草酸通过激活肾小管上皮细胞中的核因子-kappaB来诱导OPN的表达。此外，我们还研究了N-乙酰-L半胱氨酸(NAC)对人肾小管上皮细胞系中核因子-kappaB活化的抑制作用。方法：所有实验均以人肾小管上皮细胞为实验对象，人近端肾小管上皮细胞系为人乳头瘤病毒16E6/E7基因转导永生化的人近端肾小管上皮细胞。在细胞摄取0.5 mM草酸后进行总蛋白的时间依赖性提取。结果：草酸刺激后，核内p65亚单位数量显著增加(P<0.05)，NAC显著抑制p65向核内移位(P<；0.05)。结论：NAC可作为预防结石形成的药物。
Objective: The transcription factor nuclear factor-kappa B (NF-kappa B) is involved in inflammatory and immune responses through the induction of various cytokines and growth factors. Recently, the coordinated action of NF-kappa B and activator protein-1 was reported in osteopontin (OPN) expression. In the present study, we demonstrated that oxalate induces OPN expression by activating NF-kappa B in renal tubular cells. Furthermore, we investigated the inhibitory effect of N-acetyl-L-cysteine (NAC) on NF-kappa B activation in the human renal tubular cell line.Methods: All of the experiments were carried out using human kidney-2 cells, which are human proximal tubular epithelial cells immortalized by transduction with the human papillomavirus 16E6/E7 gene. The time-dependent extraction of total protein was performed after the uptake of 0.5 mM oxalate by the cells. The NF-kappa B activation and OPN expression were examined by western blotting and immunocytochemistry.Results: As a result of oxalate stimulation, the amount of p65 subunit in the nucleus increased significantly (P < 0.05), and NAC significantly inhibited the translocation of p65 into the nucleus (P < 0.05).Conclusion: These observations indicate that NAC can be used as a drug to prevent stone formation.