Activation of nuclear factor-κB pathway is responsible for tumor necrosis factor-a-induced up-regulation of endothelin B2 receptor expression in vascular smooth muscle cells in vitro

作者：Zhang, Wei; Li, Xue-Jun^*; Zeng, Xin; Shen, Dong-Yan; Liu, Chang-Qin; Zhang, Hui-Jie; Xu, Cang-Bao; Li, Xiao-Ying

来源：Toxicology Letters, 2012, 209(2): 107-112.

DOI：10.1016/j.toxlet.2011.12.005

• Tumor necrosis factor-alpha
• Endothelin B2 receptor
• Nuclear factor-kappa B
• Vascular smooth muscle cell

The endothelin B2 (ETB2) receptors are induced in vascular smooth muscle cells (VSMCs) in cardiovascular diseases. We tested if in vitro short-term exposure to the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) could up-regulate ETB2 receptors in rat mesenteric arteries, and if this effect is through activation of intracellular nuclear factor-kappa B (NF-kappa B) pathway. The mesenteric arteries were dissected from male Sprague-Dawley rats and the endothelium was removed. The arteries were co-incubated with TNF-alpha in serum-free Dulbecco's modified Eagle's medium. Real-time reverse transcription-PCR, Western blot and immunohistochemical staining were employed to assess the mRNA/protein expression of ETB2 receptors and activation of NF-kappa B pathway. The results showed that, during organ culture. TNF-alpha concentration-dependently enhanced ET52 receptors expression at both mRNA and protein levels, paralleled with activation of NF-kappa B pathway in VSMC. The up-regulated ETB2 receptor expression and NF-kappa B activation could be effectively suppressed by general transcriptional inhibitor actinomycin D, or either of the selective I kappa B kinase inhibitors wedelolactone and IMD-0354. Conclusively, the activation of intracellular NF-kappa B pathway is responsible for the up-regulation of ETB2 receptors induced by short-term exposure to TNF-alpha. This could partly explain the toxic effects of TNF-alpha on VSMCs that account for cardiovascular diseases.

• 出版日期2012-3-7
• 单位上海市闵行区中心医院; 上海交通大学; 厦门大学