Acetaldehyde-induced interleukin-1β and tumor necrosis factor-α production is inhibited by berberine through nuclear factor-κB signaling pathway in HepG2 cells
Acetaldehyde-induced interleukin-1β and tumor necrosis factor-α production is inhibited by berberine through nuclear factor-κB signaling pathway in HepG2 cells
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DOI：
10.1007/s11373-005-9003-4
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发表时间：
2005-10-01
影响因子：
11
通讯作者：
Ho, TY
中科院分区：
文献类型：
--
作者：
Hsiang, CY;Wu, SL;Ho, TY
酒精性肝病（ALD）是世界上最常见的肝病之一。促炎细胞因子水平的增加，包括白细胞介素-1 β（IL-1 β）和肿瘤坏死因子-α（TNF-α），与ALD患者相关。然而，酒精在诱导IL-1 β和TNF-α中的直接作用尚未阐明。在这项研究中，我们证明了乙醇的代谢产物乙醛能够诱导HepG 2细胞中IL-1 β和TNF-α的产生。核因子-κ B（NF-κ B）是参与调节细胞因子产生的转录因子，也被乙醛通过抑制κ B-α（I κ B-α）磷酸化和降解激活。然而，NF-κ B抑制剂，如阿司匹林，环孢素A和地塞米松，抑制乙酰丙酮酸诱导的NF-κ B活性和诱导的细胞因子产生。因此，这些数据表明，乙醛通过调节NF-κ B信号通路刺激IL-1 β和TNF-α的产生。通过筛选台湾中医药委员会监管的297种对照中草药，我们发现黄连（黄连）和黄柏（黄柏）能够抑制乙酰丙酮酸诱导的NF-κ B B活性。小檗碱，这些草药的主要成分，消除乙酰丙酮酸诱导的NF-κ B活性和细胞因子的产生，以剂量依赖性的方式。此外，其抑制能力是通过抑制诱导的I κ B-α磷酸化和降解。总之，我们首先将乙酰丙酮诱导的NF-κ B活性与HepG 2细胞中诱导的促炎细胞因子产生联系起来。我们的研究结果还表明黄连素在治疗ALD中的潜在作用。
Alcoholic liver disease (ALD) is one of the most common liver diseases in the world. Increased levels of proinflammatory cytokines, including interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha), have been correlated with the patients affected by ALD. However, the direct effect of alcohol in the induction of IL-1 beta and TNF-alpha has not been clarified. In this study, we demonstrated that acetaldehyde, the metabolic product of ethanol, was able to induce IL-1 beta and TNF-alpha production in HepG2 cells. Nuclear factor-kappa B (NF-kappa B), the transcription factor involved in the regulation of cytokine production, was also activated by acetaldehyde through inhibitory kappa B-alpha (I kappa B-alpha) phosphorylation and degradation. However, the NF-kappa B inhibitors, such as aspirin, cyclosporin A and dexamethasone, inhibited both the acetaldehyde-induced NF-kappa B activity and the induced cytokine production. Therefore, these data suggested that acetaldehyde stimulated IL-1 beta and TNF-alpha production via the regulation of NF-kappa B signaling pathway. By screening 297 controlled Chinese medicinal herbs supervised by Committee on Chinese Medicine and Pharmacy at Taiwan, we found that Coptis chinensis (Huang-Lien) and Phellodendron amurense (Huang-Po) were capable of inhibiting acetaldehyde-induced NF-kappa B activity. Berberine, the major ingredient of these herbs, abolished acetaldehyde-induced NF-kappa B activity and cytokine production in a dose-dependent manner. Moreover, its inhibitory ability was through the inhibition of induced I kappa B-alpha phosphorylation and degradation. In conclusion, we first linked the acetaldehyde-induced NF-kappa B activity to the induced proinflammatory cytokine production in HepG2 cells. Our findings also suggested the potential role of berberine in the treatment of ALD.