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

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.