RGD Reference Report - Direct effects of interleukin-13 on epithelial cells cause airway hyperreactivity and mucus overproduction in asthma. - Rat Genome Database

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

Authors: Kuperman, DA  Huang, X  Koth, LL  Chang, GH  Dolganov, GM  Zhu, Z  Elias, JA  Sheppard, D  Erle, DJ 
Citation: Kuperman DA, etal., Nat Med. 2002 Aug;8(8):885-9. Epub 2002 Jul 1.
RGD ID: 4145664
Pubmed: PMID:12091879   (View Abstract at PubMed)
DOI: DOI:10.1038/nm734   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
IL13Humanasthma  ISOIl13 (Mus musculus) RGD 
Il13Ratasthma  ISOIl13 (Mus musculus) RGD 
Il13Mouseasthma  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Il13  (interleukin 13)

Genes (Mus musculus)
Il13  (interleukin 13)

Genes (Homo sapiens)
IL13  (interleukin 13)


Additional Information