Direct effects of interleukin-13 on epithelial cells cause airway hyperreactivity and mucus overproduction in asthma.

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. AHR and mucus overproduction are consistently linked to asthma symptoms and morbidity. Asthma is mediated by Th2 lymphocytes, 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, 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. Furthermore, IL-13 delivery to the airway causes all of these effects. 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.

• Authors: Douglas A Kuperman, Xiaozhu Huang, Laura L Koth, Grace H Chang, Gregory M Dolganov, Zhou Zhu, Jack A Elias, Dean Sheppard, David J Erle
• Journal: Nature medicine (Nat Med) Vol. 8 Issue 8 Pg. 885-9 (Aug 2002) ISSN: 1078-8956 [Print] United States
• PMID: 12091879 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Interleukin-13
• STAT6 Transcription Factor
• STAT6 protein, human
• Stat6 protein, mouse
• Trans-Activators

Topics

• Animals
• Asthma (pathology, physiopathology)
• Bronchial Hyperreactivity (pathology, physiopathology)
• Epithelial Cells (pathology)
• Humans
• In Situ Hybridization
• Interleukin-13 (genetics, physiology)
• Lung (metabolism, pathology)
• Mice
• Mice, Inbred Strains
• Mice, Transgenic
• Mucus (metabolism)
• STAT6 Transcription Factor
• Signal Transduction (physiology)
• Trans-Activators (genetics, metabolism)