IL-1{beta} Induced Transcriptional Up-regulation of Bradykinin B1 and B2 Receptors in Murine Airways.
(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:
https://lup.lub.lu.se/record/164628
- author
- Zhang, Yaping LU ; Adner, Mikael LU and Cardell, Lars-Olaf LU
- organization
- publishing date
- 2007
- 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
- pmid:17255557
- 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
- 2016-04-01 12:04:22
- date last changed
- 2022-04-13 05:43:23
@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}}, keywords = {{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}}, doi = {{10.1165/rcmb.2005-0369OC}}, volume = {{36}}, year = {{2007}}, }