Background IL-4 is believed to play a role in asthma and chronic obstructive pulmonary disease through promotion of eosinophilic inflammation and mucus hypersecretion. Whether IL-4 can induce a direct effect on airway smooth muscle remains unknown.
Objective To investigate the effect of IL-4 on airway smooth muscle, focusing on the contractile response to des-Arg9-bradykinin and bradykinin.
Methods Tracheal segments from murine airways were cultured for 1–8 days in the absence and presence of IL-4. The smooth muscle response induced by des-Arg9-bradykinin and bradykinin was investigated in myographs. Expression levels for the IL-4-, bradykinin B1- and B2-receptors were characterized using RT-PCR. Specific inhibitors were used to study signal changes along the IL-4 receptor- (IL-4R-) coupled mitogen-activated protein (MAP) kinase (MAPK) pathways.
Results IL-4 treatment increased the contractile response to des-Arg9-bradykinin and bradykinin in a concentration- and time-dependent manner. Dexamethasone and the transcriptional inhibitor actinomycin D blocked this effect. c-Jun N-terminal kinase inhibitor SP600125 also blocked the effect of both des-Arg9-bradykinin and bradykinin, whereas p38 inhibitor SB203580 blocked only the former and the MAPKK inhibitor PD098059, only the latter agonist responses. IL-4 treatment increased the mRNA levels representing bradykinin B1- but not B2-receptors. Levels of IL-4R were not altered during culture.
Conclusion Long-term exposure to IL-4 increases the contractile response induced by des-Arg9-bradykinin and bradykinin in cultured murine airways. This effect appears to be mediated via an up-regulation of B1-receptors and altered signalling along the MAPK pathways.
If you can't find a tool you're looking for, please click the link at the top of the page to go "Back to old version". We'll be adding more features regularly and your feedback is important to us, so please let us know if you have comments or ideas for improvement.