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| Direct effects of interleukin-13 on epithelial cells cause airway hyperreactivity and mucus overproduction in asthma |
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| Author(s): Kuperman DA, Huang XZ, Koth LL, Chang GH, Dolganov GM, Zhu Z, Elias JA, Sheppard D, Erle DJ |
| Source: NATURE MEDICINE Volume: 8 Issue: 8 Pages: 885-889 Published: AUG 2002 |
| Times Cited: 268 References: 26 |
| Abstract: Asthma is an increasingly common disease that remains poorly understood and difficult to manage. This disease is characterized by airway hyperreactivity (AHR, defined by exaggerated airflow obstruction in response to bronchoconstrictors), mucus overproduction and chronic eosinophilic inflammation(1). AHR and mucus overproduction are consistently linked to asthma symptoms and morbidity(2,3). Asthma is mediated by Th2 lymphocytes(4-7), which produce a limited repertoire of cytokines, including interleukin-4 (IL-4), IL-5, IL-9 and IL-13. Although each of these cytokines has been implicated in asthma(4,5,7-11), IL-13 is now thought to be especially critical. In animal models of allergic asthma, blockade of IL-13 markedly inhibits allergen-induced AHR, mucus production and eosinophilia(10,11). Furthermore, IL-13 delivery to the airway causes all of these effects(10,11). IL-13 is thus both necessary and sufficient for experimental models of asthma. However, the IL-13-responsive cells causing these effects have not been identified. Here we show that mice lacking signal transducer and activator of transcription 6 (STAT6) were protected from all pulmonary effects of IL-13. Reconstitution of STAT6 only in epithelial cells was sufficient for IL-13-induced AHR and mucus production in the absence of inflammation, fibrosis or other lung pathology. These results demonstrate the importance of direct effects of IL-13 on epithelial cells in causing two central features of asthma. |
| Document Type: Article |
| Language: English |
| Reprint Address: Erle, DJ (reprint author), Univ Calif San Francisco, Sch Med, Dept Med, Lung Biol Ctr, San Francisco, CA 94143 USA |
Addresses:
1. Univ Calif San Francisco, Sch Med, Dept Med, Lung Biol Ctr, San Francisco, CA 94143 USA
2. Univ Calif San Francisco, Sch Med, Cardiovasc Res Inst, San Francisco, CA 94143 USA
3. Univ Calif San Francisco, Sch Med, Program Immunol, San Francisco, CA USA
4. Yale Univ, Sch Med, Dept Internal Med, Pulm & Crit Care Med Sect, New Haven, CT 06510 USA |
| Publisher: NATURE PUBLISHING GROUP, 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental |
| IDS Number: 579WJ |
| ISSN: 1078-8956 |
| DOI: 10.1038/nm734 |
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