Rationale: Hyperresponsiveness to bronchoconstrictor stimuli is a major pathophysiological feature of asthma, but the molecular mechanisms behind this are not fully understood. The release of tumour necrosis factor-alpha (TNF-) and interleukin-1 beta (IL-1), during the inflammatory process, is believed to play an important role in airway hyperresponsiveness. Methods: We have previously, using a murine in-vitro model of chronic airway inflammation, demonstrated that TNF- up-regulated bradykinin B₁ and B₂ receptors in the airway smooth muscle. By using the same model, the present study was designed to investigate the effects of IL-1 and its interaction with TNF- on the expression of bradykinin B₁ and B₂ receptors in mouse tracheal smooth muscle. Results: IL-1 up-regulated bradykinin B₁ and B₂ receptor mRNA expression and increased contractile response to bradykinin B₁ and B₂ receptor agonists (des-Arg⁹-bradykinin and bradykinin, respectively) in the tracheal smooth muscle. Transcriptional inhibitor actinomycin D, c-Jun N-terminal kinase (JNK) 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 transcriptional mechanism and intracellular JNK signal transduction pathway were involved. In addition, IL-1 did not affect bradykinin B₁ and B₂ receptor mRNA stability. Remicade®, an anti-TNF- antibody, markedly suppressed IL-1-induced up-regulation of bradykinin B₁ and B₂ receptors, suggesting that TNF- was involved in the up-regulation, which is further supported by that IL-1 enhanced TNF- mRNA expression in the tracheae. Conclusions: Intracellular JNK pathway and TNF- might provide key links between inflammatory mediators like IL-1 and airway hyperresponsiveness to bradykinin.