Up-regulation of bradykinin receptors in a murine in-vitro model of chronic airway inflammation

Eur J Pharmacol. 2004 Apr 5;489(1-2):117-26. doi: 10.1016/j.ejphar.2004.02.033.


Tumour necrosis factor-alpha (TNF-alpha) is a mediator with a likely role in chronic airway inflammation and airway hyperresponsiveness. In the present study, mouse tracheal segments were cultured for 1, 4 or 8 days in the absence and presence of TNF-alpha. Contractile response of cultured segments to des-Arg9-bradykinin and bradykinin was assessed in myographs and mRNA for bradykinin B1 and B2 receptors was quantified by real-time polymerase chain reaction. Both contraction to des-Arg9-bradykinin and bradykinin, mediated via bradykinin B1 and B2 receptors, respectively, and mRNA levels for these receptors were up-regulated following culture. These responses were markedly increased in segments treated with TNF-alpha. Experiments with SP600125 (anthrax(1,9-cd)pyrazol-6(2H)-one) and PD98059 (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one) demonstrated that both intracellular c-Jun N-terminal kinase and extracellular signal-regulated kinase 1/2 pathways were implicated in this process. Thus, TNF-alpha causes an increase of bradykinin contractility in mouse trachea, which at least partly is due to a transcriptional increase of bradykinin receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology
  • Animals
  • Bradykinin / analogs & derivatives*
  • Bradykinin / pharmacology
  • Bronchodilator Agents / pharmacology
  • Chronic Disease
  • Enzyme Inhibitors / pharmacology
  • Inflammation / metabolism*
  • Inflammation Mediators / pharmacology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mitogen-Activated Protein Kinases / metabolism
  • Muscle, Smooth / drug effects
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Organ Culture Techniques
  • RNA, Messenger / biosynthesis
  • Receptor, Bradykinin B1 / biosynthesis
  • Receptor, Bradykinin B2 / biosynthesis
  • Receptors, Bradykinin / biosynthesis*
  • Respiratory Tract Diseases / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Trachea / drug effects
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation / drug effects*


  • Angiotensin-Converting Enzyme Inhibitors
  • Bronchodilator Agents
  • Enzyme Inhibitors
  • Inflammation Mediators
  • RNA, Messenger
  • Receptor, Bradykinin B1
  • Receptor, Bradykinin B2
  • Receptors, Bradykinin
  • Tumor Necrosis Factor-alpha
  • bradykinin, des-Arg(9)-
  • Nitric Oxide Synthase
  • Mitogen-Activated Protein Kinases
  • Bradykinin