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Cytokines and growth factors modify the upregulation of contractile endothelin ET(A) and ET(B) receptors in rat cerebral arteries after organ culture.

Ahnstedt, Hilda LU ; Stenman, Emelie LU ; Cao, Lei LU ; Henriksson, Marie and Edvinsson, Lars LU (2012) In Acta Physiologica 205(2). p.266-278
Abstract
Aim: Experimental cerebral ischemia and organ culture of cerebral arteries induce an increased endothelin ET(B) receptor-mediated contraction. The aim of the present study was to examine if cytokines and growth factors, known to be activated in ischemia, can influence the expression and function of endothelin receptors after organ culture. Methods: Rat middle cerebral arteries were cultured for 24 h at 37°C in humidified 5% CO(2) and air in culture medium alone, or with tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), platelet-derived growth factor (PDGF), epidermal growth factor (EGF) or basic fibroblast growth factor (bFGF). Concentration-response curves were obtained for sarafotoxin 6c (ET(B) receptor agonist) and endothelin-1... (More)
Aim: Experimental cerebral ischemia and organ culture of cerebral arteries induce an increased endothelin ET(B) receptor-mediated contraction. The aim of the present study was to examine if cytokines and growth factors, known to be activated in ischemia, can influence the expression and function of endothelin receptors after organ culture. Methods: Rat middle cerebral arteries were cultured for 24 h at 37°C in humidified 5% CO(2) and air in culture medium alone, or with tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), platelet-derived growth factor (PDGF), epidermal growth factor (EGF) or basic fibroblast growth factor (bFGF). Concentration-response curves were obtained for sarafotoxin 6c (ET(B) receptor agonist) and endothelin-1 (here ET(A) receptor agonist, because of ET(B) receptor desensitization). The receptor mRNA expression was examined by real-time PCR and the protein expression by immunohistochemistry and Western blot. Results: TNF-α (100 ng/ml) and EGF (20 ng/ml) potentiated the ET(B) receptor-mediated contraction (increase in pEC(50) without change in E(max) ). bFGF (10 ng/ml) and IL-1β (10 ng/ml) induced an enhanced ET(A) receptor-mediated contraction. bFGF (10 ng/ml) significantly increased the ET(B) mRNA level, and EGF (20 ng/ml) increased the ET(A) receptor protein. Increased ET(B) receptor mRNA and protein level also were observed after treatment with IL-1β (10 ng/ml). Conclusion: The present study show that TNF-α, IL-1β, EGF and bFGF can modify the expression and function of endothelin receptors during organ culture. Since there is similar receptor upregulation in experimental stroke, the effect of cytokines and growth factors on endothelin receptor upregulation is an interesting aspect to study in vivo. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
keywords
endothelin receptors, basic fibroblast growth factor, epidermal growth, factor, interleukin-1 ss, platelet-derived growth factor, tumour, necrosis factor-a
in
Acta Physiologica
volume
205
issue
2
pages
266 - 278
publisher
Wiley-Blackwell
external identifiers
  • wos:000303115100009
  • pmid:22145714
  • scopus:84860249292
ISSN
1748-1708
DOI
10.1111/j.1748-1716.2011.02392.x
language
English
LU publication?
yes
id
2da5a84d-8cbd-48ba-9e08-70a0f08e03b0 (old id 2274392)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22145714?dopt=Abstract
date added to LUP
2012-01-03 13:14:37
date last changed
2017-09-10 03:17:56
@article{2da5a84d-8cbd-48ba-9e08-70a0f08e03b0,
  abstract     = {Aim: Experimental cerebral ischemia and organ culture of cerebral arteries induce an increased endothelin ET(B) receptor-mediated contraction. The aim of the present study was to examine if cytokines and growth factors, known to be activated in ischemia, can influence the expression and function of endothelin receptors after organ culture. Methods: Rat middle cerebral arteries were cultured for 24 h at 37°C in humidified 5% CO(2) and air in culture medium alone, or with tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), platelet-derived growth factor (PDGF), epidermal growth factor (EGF) or basic fibroblast growth factor (bFGF). Concentration-response curves were obtained for sarafotoxin 6c (ET(B) receptor agonist) and endothelin-1 (here ET(A) receptor agonist, because of ET(B) receptor desensitization). The receptor mRNA expression was examined by real-time PCR and the protein expression by immunohistochemistry and Western blot. Results: TNF-α (100 ng/ml) and EGF (20 ng/ml) potentiated the ET(B) receptor-mediated contraction (increase in pEC(50) without change in E(max) ). bFGF (10 ng/ml) and IL-1β (10 ng/ml) induced an enhanced ET(A) receptor-mediated contraction. bFGF (10 ng/ml) significantly increased the ET(B) mRNA level, and EGF (20 ng/ml) increased the ET(A) receptor protein. Increased ET(B) receptor mRNA and protein level also were observed after treatment with IL-1β (10 ng/ml). Conclusion: The present study show that TNF-α, IL-1β, EGF and bFGF can modify the expression and function of endothelin receptors during organ culture. Since there is similar receptor upregulation in experimental stroke, the effect of cytokines and growth factors on endothelin receptor upregulation is an interesting aspect to study in vivo.},
  author       = {Ahnstedt, Hilda and Stenman, Emelie and Cao, Lei and Henriksson, Marie and Edvinsson, Lars},
  issn         = {1748-1708},
  keyword      = {endothelin receptors,basic fibroblast growth factor,epidermal growth,factor,interleukin-1 ss,platelet-derived growth factor,tumour,necrosis factor-a},
  language     = {eng},
  number       = {2},
  pages        = {266--278},
  publisher    = {Wiley-Blackwell},
  series       = {Acta Physiologica},
  title        = {Cytokines and growth factors modify the upregulation of contractile endothelin ET(A) and ET(B) receptors in rat cerebral arteries after organ culture.},
  url          = {http://dx.doi.org/10.1111/j.1748-1716.2011.02392.x},
  volume       = {205},
  year         = {2012},
}