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

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

Toxicology letters (2011-12-31)
Wei Zhang, Xue-Jun Li, Xin Zeng, Dong-Yan Shen, Chang-Qin Liu, Hui-Jie Zhang, Cang-Bao Xu, Xiao-Ying Li
ABSTRACT

The endothelin B2 (ET(B2)) 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-α (TNF-α) could up-regulate ET(B2) receptors in rat mesenteric arteries, and if this effect is through activation of intracellular nuclear factor-κB (NF-κB) pathway. The mesenteric arteries were dissected from male Sprague-Dawley rats and the endothelium was removed. The arteries were co-incubated with TNF-α 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 ET(B2) receptors and activation of NF-κB pathway. The results showed that, during organ culture, TNF-α concentration-dependently enhanced ET(B2) receptors expression at both mRNA and protein levels, paralleled with activation of NF-κB pathway in VSMC. The up-regulated ET(B2) receptor expression and NF-κB activation could be effectively suppressed by general transcriptional inhibitor actinomycin D, or either of the selective IκB kinase inhibitors wedelolactone and IMD-0354. Conclusively, the activation of intracellular NF-κB pathway is responsible for the up-regulation of ET(B2) receptors induced by short-term exposure to TNF-α. This could partly explain the toxic effects of TNF-α on VSMCs that account for cardiovascular diseases.

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Sigma-Aldrich
Wedelolactone, ≥98% (HPLC), powder