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

Zhang, Wei; Li, Xue-Jun; Zeng, Xin; Shen, Dong-Yan; Liu, Chang-Qin; Zhang, Hui-Jie; Xu, Cang-Bao LU and Li, Xiao-Ying (2012) In Toxicology Letters 209(2). p.107-112
Abstract
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... (More)
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. (C) 2011 Elsevier Ireland Ltd. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
factor-kappa B, Vascular smooth muscle cell, Nuclear, Tumor necrosis factor-alpha, Endothelin B2 receptor
in
Toxicology Letters
volume
209
issue
2
pages
107 - 112
publisher
Elsevier
external identifiers
  • wos:000301277200001
  • scopus:84862799831
ISSN
1879-3169
DOI
10.1016/j.toxlet.2011.12.005
language
English
LU publication?
yes
id
810f858f-a85c-42b4-8c62-3933946d8cbe (old id 2515569)
date added to LUP
2012-05-07 08:35:50
date last changed
2017-01-29 03:40:21
@article{810f858f-a85c-42b4-8c62-3933946d8cbe,
  abstract     = {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. (C) 2011 Elsevier Ireland Ltd. All rights reserved.},
  author       = {Zhang, Wei and Li, Xue-Jun and Zeng, Xin and Shen, Dong-Yan and Liu, Chang-Qin and Zhang, Hui-Jie and Xu, Cang-Bao and Li, Xiao-Ying},
  issn         = {1879-3169},
  keyword      = {factor-kappa B,Vascular smooth muscle cell,Nuclear,Tumor necrosis factor-alpha,Endothelin B2 receptor},
  language     = {eng},
  number       = {2},
  pages        = {107--112},
  publisher    = {Elsevier},
  series       = {Toxicology Letters},
  title        = {Activation of nuclear factor-kappa B pathway is responsible for tumor necrosis factor-a-induced up-regulation of endothelin B2 receptor expression in vascular smooth muscle cells in vitro},
  url          = {http://dx.doi.org/10.1016/j.toxlet.2011.12.005},
  volume       = {209},
  year         = {2012},
}