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IL-13 receptor ?2 contributes to development of experimental allergic asthma.
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ABSTRACT: Background
IL-13 receptor ?2 (IL-13R?2) binds IL-13 with high affinity and modulates IL-13 responses. There are soluble and membrane forms of IL-13R?2 generated by alternative splicing in mice, but human subjects express only the membrane form of IL-13R?2 (memIL-13R?2).Objective
We determined the role of memIL-13R?2 in the development of allergic inflammation in mouse models of asthma.Methods
IL-13R?2-deficient and memIL-13R?2 lung epithelium-specific transgenic mice were challenged with house dust mite (HDM). Airway hyperresponsiveness (AHR) and inflammation were assessed based on the airway pressure-time index, bronchoalveolar lavage (BAL) cell counts, and lung histology. Mucus production was determined by means of periodic acid-Schiff staining of lung sections, Western blot analysis of chloride channel calcium activated 3 (CLCA3) expression in lung homogenates, and ELISA of Muc5ac in BAL fluid. The expression of cytokines and chemokines was determined by using RT-quantitative PCR.Results
In IL-13R?2-deficient mice AHR and airway inflammation were attenuated compared with levels seen in wild-type mice after HDM challenge. Lung epithelial overexpression of memIL-13R?2 in the IL-13R?2-deficient mice reconstituted AHR and inflammation to levels similar to those observed in HDM-challenged wild-type mice. Mucus production was attenuated in lungs from HDM-treated IL-13R?2-deficient mice, whereas lung epithelial overexpression of memIL-13R?2 increased mucus production. Lung epithelial overexpression of memIL-13R?2 had no effect on levels of the soluble form of IL-13R?2 in serum or BAL fluid and did not affect IL-13-dependent signal transducer and activator of transcription 6 activation in the lungs.Conclusion
These data collectively support a distinct role for memIL-13R?2 in the lung and suggest that memIL-13R?2 might contribute to allergic inflammation.
SUBMITTER: Chen W
PROVIDER: S-EPMC3836839 | biostudies-literature | 2013 Oct
REPOSITORIES: biostudies-literature
Publications
IL-13 receptor α2 contributes to development of experimental allergic asthma.
The Journal of allergy and clinical immunology 20130612 4
<h4>Background</h4>IL-13 receptor α2 (IL-13Rα2) binds IL-13 with high affinity and modulates IL-13 responses. There are soluble and membrane forms of IL-13Rα2 generated by alternative splicing in mice, but human subjects express only the membrane form of IL-13Rα2 (memIL-13Rα2).<h4>Objective</h4>We determined the role of memIL-13Rα2 in the development of allergic inflammation in mouse models of asthma.<h4>Methods</h4>IL-13Rα2-deficient and memIL-13Rα2 lung epithelium-specific transgenic mice were ...[more]
