| IL-1{beta} Induced Transcriptional Up-regulation of Bradykinin B1 and B2 Receptors in Murine Airways. | |
Abstract/OtherAbstract
:
|
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. |
Authors
:
|
Zhang, Yaping, Adner, Mikael, Cardell, Lars-Olaf |
Contributors
:
|
- |
Publication Detail
:
|
Publisher : American Thoracic Society Type : text Format : - |
Date Detail
:
|
2007 |
Subject
:
|
bradykinin, receptor, IL-1 beta, remicade, JNK, Medicine and Health Sciences |
Coverage
:
|
- |
Relation
:
|
- |
Source
:
|
- |
Copyright Information
:
|
- |
Other Details
:
|
Languages : eng |
Export Citation
:
|
APA/MLA Format Download EndNote Download BibTex |
Previous Document: (99m)Tc-DTPA Uptake and Electrical Impedance Measurements in Verification of In Vivo Electropermeabi...
Next Document: Diet and body constitution in relation to sub-groups of breast cancer defined by tumour grade, proli...