IL-13 suppresses double-stranded RNA-induced IFN-λ production in lung cells

Biochem Biophys Res Commun. 2011 Jan 28;404(4):922-7. doi: 10.1016/j.bbrc.2010.12.082. Epub 2010 Dec 22.

Abstract

Acute asthma exacerbations are frequently associated with respiratory viral infections. Although impaired production of type III IFNs (IFN-λs) is related to the severity of asthma exacerbation, the mechanisms underlying deficient IFN-λ production in asthma are poorly understood. Airway epithelial cells were stimulated in vitro with a synthetic mimetic of viral double-stranded RNA (dsRNA). IL-13, a crucial cytokine responsible for asthma pathogenesis, suppressed dsRNA-induced expression of IFN-λs, and JAK inhibitor AG490 prevented the suppression by IL-13. IL-13 per se did not affect IFN-λ production or the expressions of membrane dsRNA receptor TLR3 and of cytoplasmic receptors RIG-I and MDA5. IL-13-deficient mice exhibited more enhanced IFN-λ expression after intratracheal instillation of dsRNA than wild-type mice, whereas IFN-λ expression after dsRNA was absent in the mouse lungs of the OVA-induced asthma model. These findings suggest that IL-13 may be a putative cytokine suppressing IFN-λ production against airway viral infections in asthmatics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Asthma / immunology*
  • Asthma / virology
  • Cell Line
  • Humans
  • Interferon-gamma / biosynthesis*
  • Interleukin-13 / genetics
  • Interleukin-13 / immunology*
  • Lung / immunology*
  • Macrophages, Alveolar / immunology
  • Mice
  • Mice, Mutant Strains
  • Poly I-C / immunology
  • Poly I-C / pharmacology
  • RNA, Double-Stranded / immunology*
  • RNA, Double-Stranded / pharmacology
  • Respiratory Mucosa / immunology*
  • Virus Diseases / complications
  • Virus Diseases / immunology*

Substances

  • Interleukin-13
  • RNA, Double-Stranded
  • Interferon-gamma
  • Poly I-C