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IL-1{beta} Induced Transcriptional Up-regulation of Bradykinin B1 and B2 Receptors in Murine Airways.

Zhang, Yaping LU ; Adner, Mikael LU and Cardell, Lars-Olaf LU (2007) In American Journal of Respiratory Cell and Molecular Biology 36(6). p.697-705
Abstract
Hyperresponsiveness to bronchoconstrictor stimuli is a major pathophysiologic feature of asthma, but the molecular mechanisms behind this are not fully understood. The release of TNF-alpha and IL-1 beta during the inflammatory process is believed to play an important role in airway hyperresponsiveness. We have previously demonstrated, using a murine in vitro model of chronic airway inflammation, that TNF-alpha up-regulated bradykinin B-1 and B-2 receptors in the airway smooth muscle. By using the same model, the present study was designed to investigate the effects of IL-1 beta and its interaction with TNF-alpha on the expression of bradykinin B-1 and B-2 receptors in mouse tracheal smooth muscle. IL-1 beta up-regulated bradykinin B-1 and... (More)
Hyperresponsiveness to bronchoconstrictor stimuli is a major pathophysiologic feature of asthma, but the molecular mechanisms behind this are not fully understood. The release of TNF-alpha and IL-1 beta during the inflammatory process is believed to play an important role in airway hyperresponsiveness. We have previously demonstrated, using a murine in vitro model of chronic airway inflammation, that TNF-alpha up-regulated bradykinin B-1 and B-2 receptors in the airway smooth muscle. By using the same model, the present study was designed to investigate the effects of IL-1 beta and its interaction with TNF-alpha on the expression of bradykinin B-1 and B-2 receptors in mouse tracheal smooth muscle. IL-1 beta up-regulated bradykinin B-1 and B2 receptor expression and increased contractile response to bradykinin B-1 and B-2 receptor agonists (des-Argl-bradykinin and bradykinin, respectively) in the tracheal smooth muscle. Transcriptional inhibitor actinomycin D, c-Jun N-terminal kinase (INK) inhibitors SP600125 and TAT-TI-JIP(153-163), but not extracellular signal-regulated kinase 1 and 2 (ERK 1/2) inhibitor PD98059, significantly attenuated this up-regulation, indicating that a transcriptional mechanism and intracellular JNK signal transduction pathway were involved. In addition, IL-1 beta did not affect bradykinin B-1 and B-2 receptor mRNA stability. Remicade, an anti-TNF-a antibody, markedly suppressed IL-1 beta-incluced up-regulation of bradykinin B-1 and B-2 receptors, suggesting that TNF-alpha was involved in the up-regulation, which is further supported by the fact that IL-1 beta enhanced TNF-alpha mRNA expression in the tracheae. Intracellular INK pathway and TNF-alpha might provide key links between inflammatory mediators like IL-1 beta and airway hyperresponsiveness to bradykinin. (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
remicade, IL-1 beta, receptor, bradykinin, JNK
in
American Journal of Respiratory Cell and Molecular Biology
volume
36
issue
6
pages
697 - 705
publisher
American Thoracic Society
external identifiers
  • wos:000246991800007
  • scopus:34249900489
ISSN
1535-4989
DOI
10.1165/rcmb.2005-0369OC
language
English
LU publication?
yes
id
49e7b709-490c-459e-a0ca-5e31a322a1e0 (old id 164628)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17255557&dopt=Abstract
date added to LUP
2007-07-30 11:30:46
date last changed
2017-06-18 03:39:26
@article{49e7b709-490c-459e-a0ca-5e31a322a1e0,
  abstract     = {Hyperresponsiveness to bronchoconstrictor stimuli is a major pathophysiologic feature of asthma, but the molecular mechanisms behind this are not fully understood. The release of TNF-alpha and IL-1 beta during the inflammatory process is believed to play an important role in airway hyperresponsiveness. We have previously demonstrated, using a murine in vitro model of chronic airway inflammation, that TNF-alpha up-regulated bradykinin B-1 and B-2 receptors in the airway smooth muscle. By using the same model, the present study was designed to investigate the effects of IL-1 beta and its interaction with TNF-alpha on the expression of bradykinin B-1 and B-2 receptors in mouse tracheal smooth muscle. IL-1 beta up-regulated bradykinin B-1 and B2 receptor expression and increased contractile response to bradykinin B-1 and B-2 receptor agonists (des-Argl-bradykinin and bradykinin, respectively) in the tracheal smooth muscle. Transcriptional inhibitor actinomycin D, c-Jun N-terminal kinase (INK) inhibitors SP600125 and TAT-TI-JIP(153-163), but not extracellular signal-regulated kinase 1 and 2 (ERK 1/2) inhibitor PD98059, significantly attenuated this up-regulation, indicating that a transcriptional mechanism and intracellular JNK signal transduction pathway were involved. In addition, IL-1 beta did not affect bradykinin B-1 and B-2 receptor mRNA stability. Remicade, an anti-TNF-a antibody, markedly suppressed IL-1 beta-incluced up-regulation of bradykinin B-1 and B-2 receptors, suggesting that TNF-alpha was involved in the up-regulation, which is further supported by the fact that IL-1 beta enhanced TNF-alpha mRNA expression in the tracheae. Intracellular INK pathway and TNF-alpha might provide key links between inflammatory mediators like IL-1 beta and airway hyperresponsiveness to bradykinin.},
  author       = {Zhang, Yaping and Adner, Mikael and Cardell, Lars-Olaf},
  issn         = {1535-4989},
  keyword      = {remicade,IL-1 beta,receptor,bradykinin,JNK},
  language     = {eng},
  number       = {6},
  pages        = {697--705},
  publisher    = {American Thoracic Society},
  series       = {American Journal of Respiratory Cell and Molecular Biology},
  title        = {IL-1{beta} Induced Transcriptional Up-regulation of Bradykinin B1 and B2 Receptors in Murine Airways.},
  url          = {http://dx.doi.org/10.1165/rcmb.2005-0369OC},
  volume       = {36},
  year         = {2007},
}