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IL-13 receptor α2 contributes to development of experimental allergic asthma.
J Allergy Clin Immunol 2013; 132(4):951-8.e1-6JA

Abstract

BACKGROUND

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).

OBJECTIVE

We determined the role of memIL-13Rα2 in the development of allergic inflammation in mouse models of asthma.

METHODS

IL-13Rα2-deficient and memIL-13Rα2 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-13Rα2-deficient mice AHR and airway inflammation were attenuated compared with levels seen in wild-type mice after HDM challenge. Lung epithelial overexpression of memIL-13Rα2 in the IL-13Rα2-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-13Rα2-deficient mice, whereas lung epithelial overexpression of memIL-13Rα2 increased mucus production. Lung epithelial overexpression of memIL-13Rα2 had no effect on levels of the soluble form of IL-13Rα2 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-13Rα2 in the lung and suggest that memIL-13Rα2 might contribute to allergic inflammation.

Authors+Show Affiliations

Division of Asthma Research, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

23763980

Citation

Chen, Weiguo, et al. "IL-13 Receptor Α2 Contributes to Development of Experimental Allergic Asthma." The Journal of Allergy and Clinical Immunology, vol. 132, no. 4, 2013, pp. 951-8.e1-6.
Chen W, Sivaprasad U, Gibson AM, et al. IL-13 receptor α2 contributes to development of experimental allergic asthma. J Allergy Clin Immunol. 2013;132(4):951-8.e1-6.
Chen, W., Sivaprasad, U., Gibson, A. M., Ericksen, M. B., Cunningham, C. M., Bass, S. A., ... Khurana Hershey, G. K. (2013). IL-13 receptor α2 contributes to development of experimental allergic asthma. The Journal of Allergy and Clinical Immunology, 132(4), pp. 951-8.e1-6. doi:10.1016/j.jaci.2013.04.016.
Chen W, et al. IL-13 Receptor Α2 Contributes to Development of Experimental Allergic Asthma. J Allergy Clin Immunol. 2013;132(4):951-8.e1-6. PubMed PMID: 23763980.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - IL-13 receptor α2 contributes to development of experimental allergic asthma. AU - Chen,Weiguo, AU - Sivaprasad,Umasundari, AU - Gibson,Aaron M, AU - Ericksen,Mark B, AU - Cunningham,Christie M, AU - Bass,Stacey A, AU - Kinker,Kayla G, AU - Finkelman,Fred D, AU - Wills-Karp,Marsha, AU - Khurana Hershey,Gurjit K, Y1 - 2013/06/12/ PY - 2012/09/05/received PY - 2013/03/21/revised PY - 2013/04/05/accepted PY - 2013/6/15/entrez PY - 2013/6/15/pubmed PY - 2013/12/16/medline KW - AHR KW - APTI KW - Airway hyperresponsiveness KW - Airway pressure-time index KW - BAL KW - BALF KW - Bronchoalveolar lavage KW - Bronchoalveolar lavage fluid KW - CLCA3 KW - Chloride channel calcium activated 3 KW - EMSA KW - Electrophoretic mobility shift assay KW - HDM KW - House dust mite KW - Human growth hormone KW - IL-13 KW - IL-13 receptor KW - IL-13 receptor α1 KW - IL-13 receptor α2 KW - IL-13Rα1 KW - IL-13Rα2 KW - IL-4 receptor α KW - IL-4Rα KW - MCP KW - Membrane form of IL-13Rα2 KW - Monocyte chemoattractant protein KW - PAS KW - Periodic acid–Schiff KW - Quantitative PCR KW - Rat Clara cell 10 kDa KW - STAT6 KW - Signal transducer and activator of transcription 6 KW - Soluble form of IL-13Rα2 KW - airway hyperresponsiveness KW - airway inflammation KW - hGH KW - lung KW - memIL-13Rα2 KW - qPCR KW - rCC10 KW - sIL-13Rα2 SP - 951-8.e1-6 JF - The Journal of allergy and clinical immunology JO - J. Allergy Clin. Immunol. VL - 132 IS - 4 N2 - BACKGROUND: 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). OBJECTIVE: We determined the role of memIL-13Rα2 in the development of allergic inflammation in mouse models of asthma. METHODS: IL-13Rα2-deficient and memIL-13Rα2 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-13Rα2-deficient mice AHR and airway inflammation were attenuated compared with levels seen in wild-type mice after HDM challenge. Lung epithelial overexpression of memIL-13Rα2 in the IL-13Rα2-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-13Rα2-deficient mice, whereas lung epithelial overexpression of memIL-13Rα2 increased mucus production. Lung epithelial overexpression of memIL-13Rα2 had no effect on levels of the soluble form of IL-13Rα2 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-13Rα2 in the lung and suggest that memIL-13Rα2 might contribute to allergic inflammation. SN - 1097-6825 UR - https://www.unboundmedicine.com/medline/citation/23763980/IL_13_receptor_α2_contributes_to_development_of_experimental_allergic_asthma_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-6749(13)00663-5 DB - PRIME DP - Unbound Medicine ER -