• airway;
  • asthma;
  • bradykinin;
  • glucocorticoid;
  • hyper-responsiveness;
  • inflammation;
  • TNF-α;
  • transcription


Background Glucocorticoids are effective drugs for controlling symptoms and airway inflammation in respiratory diseases such as asthma and chronic obstructive pulmonary disease. However, the mechanisms behind their effects are not fully understood. We have recently demonstrated that prolonged exposure to the pro-inflammatory mediator tumour necrosis factor-α (TNF-α) markedly enhanced contractile responses to des-Arg9-bradykinin (selective bradykinin B1 receptor agonist) and bradykinin (selective bradykinin B2 receptor agonist) in murine airways. This increase was paralleled with elevated mRNA levels for bradykinin B1 and B2 receptors, a process involving intracellular mitogen-activated protein kinase pathways.

Objective To investigate the effects of glucocorticoids on the TNF-α up-regulated bradykinin B1 and B2 receptor response.

Methods Tracheal segments from BALB/c J mice were cultured with and without TNF-α, in the absence and presence of the transcriptional inhibitor actinomycin D or the glucocorticoid, dexamethasone. The contractile response induced by des-Arg9-bradykinin and bradykinin was subsequently assessed in a myograph system and mRNA for bradykinin B1 and B2 receptors was quantified using real-time polymerase chain reaction.

Results Actinomycin D abolished and dexamethasone concentration-dependently suppressed the TNF-α-induced enhancement of the des-Arg9-bradykinin and bradykinin responses. This was paralleled by a reduction of the mRNA expression for the bradykinin B1 and B2 receptors.

Conclusion The presented data suggests the involvement of transcriptional mechanisms in the up-regulation of bradykinin B1 and B2 receptors during asthmatic airway inflammation, as well as in their down-regulation following glucocorticoid treatment.