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-1beta 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-1beta and its interaction with TNF-alpha on the expression of bradykinin B(1) and B(2) receptors in mouse tracheal smooth muscle. IL-1beta up-regulated bradykinin B(1) and B(2) receptor expression and increased contractile response to bradykinin B(1) and B(2) receptor agonists (des-Arg(9)-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 a transcriptional mechanism and intracellular JNK signal transduction pathway were involved. In addition, IL-1beta did not affect bradykinin B(1) and B(2) receptor mRNA stability. Remicade, an anti-TNF-alpha antibody, markedly suppressed IL-1beta-induced 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-1beta enhanced TNF-alpha mRNA expression in the tracheae. Intracellular JNK pathway and TNF-alpha might provide key links between inflammatory mediators like IL-1beta and airway hyperresponsiveness to bradykinin.