Advanced

Up-regulation of bradykinin receptors in rat bronchia via IkappaB kinase-mediated inflammatory signaling pathway.

Lei, Ying LU ; Zhang, Yaping LU ; Cao, Yongxiao; Edvinsson, Lars LU and Xu, Cang-Bao LU (2010) In European Journal of Pharmacology 634(1-3). p.149-161
Abstract
IkappaB kinase (IKK)-mediated intracellular signaling mechanisms may be involved in airway hyperresponsiveness through up-regulation of bradykinin receptors. This study was designed to examine if organ culture of rat bronchial segments induces airway hyperresponsiveness to bradykinin and if inhibition of IKK can abrogate the airway hyperresponsiveness to bradykinin via suppressing the expression of bradykinin B(1) and B(2) receptors. Rat bronchi were isolated and cut into ring segments. The segments were then organ cultured in the presence or absence of IKK inhibitors, BMS-345541 or TPCA-1. des-Arg(9)-bradykinin (B(1) receptor agonist) - and bradykinin (B(2) receptor agonist) - induced contractions of the segments were monitored by a... (More)
IkappaB kinase (IKK)-mediated intracellular signaling mechanisms may be involved in airway hyperresponsiveness through up-regulation of bradykinin receptors. This study was designed to examine if organ culture of rat bronchial segments induces airway hyperresponsiveness to bradykinin and if inhibition of IKK can abrogate the airway hyperresponsiveness to bradykinin via suppressing the expression of bradykinin B(1) and B(2) receptors. Rat bronchi were isolated and cut into ring segments. The segments were then organ cultured in the presence or absence of IKK inhibitors, BMS-345541 or TPCA-1. des-Arg(9)-bradykinin (B(1) receptor agonist) - and bradykinin (B(2) receptor agonist) - induced contractions of the segments were monitored by a sensitive organ bath system. The expression of bradykinin B(1) and B(2) receptors, inflammatory mediators and phosphorylated IKK were studied by a real-time PCR and/or by immunohistochemistry using confocal microscopy. Organ culture of the bronchial segments induced a time-dependent up-regulation of bradykinin B(1) and B(2) receptors. The IKK inhibitors abolished the organ culture-induced up-regulation of bradykinin B(1) and B(2) receptor-mediated contractions in a concentration-dependent manner. This was paralleled with inhibition of IKK activity (phosphorylation), reduced mRNA and protein expressions of bradykinin B(1) and B(2) receptors and decreased mRNA expression of inflammatory mediators (interleukin-6, inducible nitric oxide synthase, cyclooxygenase 2 and matrix metalloproteinase 9). Our results show that organ culture induces IKK-mediated inflammatory changes in airways which subsequently results in airway hyperresponsiveness to bradykinin via the up-regulated bradykinin receptors. Thus, IKK inhibition might be a promising approach for treatment of airway inflammation and airway hyperresponsiveness that are often seen in asthmatic patients. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Receptor, Inflammatory mediator, I kappa B kinase, Bradykinin, BMS-345541, TPCA-1
in
European Journal of Pharmacology
volume
634
issue
1-3
pages
149 - 161
publisher
Elsevier
external identifiers
  • pmid:20184874
  • wos:000277554900022
  • scopus:77951177701
ISSN
1879-0712
DOI
10.1016/j.ejphar.2010.02.020
language
English
LU publication?
yes
id
fe14ba20-8be7-4523-af5a-ad2a782af23a (old id 1582855)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20184874?dopt=Abstract
date added to LUP
2010-04-06 17:05:04
date last changed
2018-05-29 10:07:50
@article{fe14ba20-8be7-4523-af5a-ad2a782af23a,
  abstract     = {IkappaB kinase (IKK)-mediated intracellular signaling mechanisms may be involved in airway hyperresponsiveness through up-regulation of bradykinin receptors. This study was designed to examine if organ culture of rat bronchial segments induces airway hyperresponsiveness to bradykinin and if inhibition of IKK can abrogate the airway hyperresponsiveness to bradykinin via suppressing the expression of bradykinin B(1) and B(2) receptors. Rat bronchi were isolated and cut into ring segments. The segments were then organ cultured in the presence or absence of IKK inhibitors, BMS-345541 or TPCA-1. des-Arg(9)-bradykinin (B(1) receptor agonist) - and bradykinin (B(2) receptor agonist) - induced contractions of the segments were monitored by a sensitive organ bath system. The expression of bradykinin B(1) and B(2) receptors, inflammatory mediators and phosphorylated IKK were studied by a real-time PCR and/or by immunohistochemistry using confocal microscopy. Organ culture of the bronchial segments induced a time-dependent up-regulation of bradykinin B(1) and B(2) receptors. The IKK inhibitors abolished the organ culture-induced up-regulation of bradykinin B(1) and B(2) receptor-mediated contractions in a concentration-dependent manner. This was paralleled with inhibition of IKK activity (phosphorylation), reduced mRNA and protein expressions of bradykinin B(1) and B(2) receptors and decreased mRNA expression of inflammatory mediators (interleukin-6, inducible nitric oxide synthase, cyclooxygenase 2 and matrix metalloproteinase 9). Our results show that organ culture induces IKK-mediated inflammatory changes in airways which subsequently results in airway hyperresponsiveness to bradykinin via the up-regulated bradykinin receptors. Thus, IKK inhibition might be a promising approach for treatment of airway inflammation and airway hyperresponsiveness that are often seen in asthmatic patients.},
  author       = {Lei, Ying and Zhang, Yaping and Cao, Yongxiao and Edvinsson, Lars and Xu, Cang-Bao},
  issn         = {1879-0712},
  keyword      = {Receptor,Inflammatory mediator,I kappa B kinase,Bradykinin,BMS-345541,TPCA-1},
  language     = {eng},
  number       = {1-3},
  pages        = {149--161},
  publisher    = {Elsevier},
  series       = {European Journal of Pharmacology},
  title        = {Up-regulation of bradykinin receptors in rat bronchia via IkappaB kinase-mediated inflammatory signaling pathway.},
  url          = {http://dx.doi.org/10.1016/j.ejphar.2010.02.020},
  volume       = {634},
  year         = {2010},
}