Phytoestrogen bavachin mediates anti-inflammation targeting IκB kinase-IκBα-NF-κB signaling pathway in chondrocytes in vitro
Phytoestrogen bavachin mediates anti-inflammation targeting IκB kinase-IκBα-NF-κB signaling pathway in chondrocytes in vitro
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DOI：
10.1016/j.ejphar.2010.03.031
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发表时间：
2010-06-25
影响因子：
5
通讯作者：
Ho, Ling-Jun
中科院分区：
文献类型：
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作者：
Cheng, Cheng-Chung;Chen, Yi-Hsin;Ho, Ling-Jun
促炎细胞因子白介素-1β (IL-1β) 在骨关节炎的发病机制中发挥着关键作用。尽管雌激素对骨关节炎患者的软骨有保护作用，但它也可能增加中风和癌症的风险。作为天然雌激素受体调节剂的植物雌激素可以作为替代品。本研究旨在鉴定具有抗炎特性并可能作为潜在软骨保护化合物的药用植物雌激素。本研究使用人类软骨细胞和软骨细胞系 CHON-002。分别通过ELISA或Western印迹测量蛋白质浓度或表达。分别通过电泳迁移率变动测定和双荧光素酶报告基因测定评估转录因子的DNA结合活性和转录活性。通过趋化性测定分析细胞迁移。我们发现，在筛选的植物雌激素中，补骨脂二氢黄酸甲酯可以有效降低 IL-1 β 诱导的核因子 kappa B (NF-kappa B)，但不能降低激活蛋白 1 (AP-1) DNA 结合活性。 Bavachin 还抑制 I kappa B α 降解、增加 p65 和 p50 的核转位以及降低 I kappa B α 激酶 (IKK) 活性。此外，巴瓦钦抑制 IL-1 β 诱导的趋化因子产生，导致 THP-1 单核细胞迁移减少。我们的结果表明，通过减少 IL-1 β 诱导的 IKK-I kappa B α-NF-kappa B 信号通路激活，补骨脂黄素可能保护骨关节炎患者关节软骨免受炎症介导的损伤。 (C) 2010 Elsevier B.V. 保留所有权利。
The pro-inflammatory cytokine interleukin-1beta (IL-1 beta) plays critical roles in pathogenesis of osteoarthritis. Although estrogen is protective for cartilage in osteoarthritis patients, it also potentially increases the risk of stroke and cancer. Phytoestrogens acting as natural estrogen receptor modulators may serve as alternatives. This study aimed to identify medicinal phytoestrogens that preserve anti-inflammatory property and may function as potential chondro-protective compounds. Both human chondrocytes and chondrocytic cell line CHON-002 were used for this study. Protein concentrations or expressions were measured by ELISA or Western blot, respectively. The DNA-binding activity and transcriptional activity of transcription factors were evaluated by electrophoretic mobility shift assay and dual-luciferase reporter assay, respectively. Cell migration was analyzed by chemotaxis assays. We found that among screened phytoestrogens, bavachin could potently decrease IL-1 beta-induced nuclear factor-kappa B (NF-kappa B) but not activator protein-1 (AP-1) DNA-binding activity. Bavachin also inhibited I kappa B alpha degradation, increased nuclear translocation of p65 and p50 as well as decreased I kappa B alpha kinase (IKK) activity. Furthermore, bavachin inhibited IL-1 beta-induced chemokine production that resulted in reduced migration of THP-1 monocytic cells. Our results suggest that through decreasing IL-1 beta-induced activation of IKK-I kappa B alpha-NF-kappa B signaling pathway, bavachin potentially protects cartilage from inflammation-mediated damage in joints of osteoarthritis patients. (C) 2010 Elsevier B.V. All rights reserved.