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Clinical & Experimental Allergy

Interleukin-4 increases murine airway response to kinins, via up-regulation of bradykinin B1-receptors and altered signalling along mitogen-activated protein kinase pathways

Authors

  • M. Bryborn,

    1. Laboratory of Clinical and Experimental Allergy, Department of Otorhinolaryngology, Malmö University Hospital, Lund University, Malmö, Sweden
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  • M. Adner,

    1. Laboratory of Clinical and Experimental Allergy, Department of Otorhinolaryngology, Malmö University Hospital, Lund University, Malmö, Sweden
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  • L.-O. Cardell

    1. Laboratory of Clinical and Experimental Allergy, Department of Otorhinolaryngology, Malmö University Hospital, Lund University, Malmö, Sweden
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Malin Bryborn, Laboratory of Clinical and Experimental Allergy, Department of Otorhinolaryngology, Malmö University Hospital, SE-205 02 Malmö, Sweden. E-mail: malin.bryborn@oron.mas.lu.se

Summary

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.

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