Signal transducer and activator of transcription 6 (STAT-6) expression and function in asthmatic bronchial epithelium

J Allergy Clin Immunol. 2001 Nov;108(5):832-8. doi: 10.1067/mai.2001.119554.

Abstract

Background: Asthma is associated with increased production of IL-4 and IL-13.

Objective: Because many of the effects of these cytokines are mediated by activation of signal transducer and activator of transcription 6 (STAT-6), we investigated expression and function of this transcription factor in the airways.

Methods: STAT-6 expression was investigated through use of immunohistochemistry or RT-PCR applied to bronchial biopsy specimens or brushings from normal control or asthmatic subjects. STAT-6 function was investigated by means of Western blotting and ELISA applied to primary epithelial cell cultures.

Results: Immunohistochemistry revealed that the bronchial epithelium was the major site of STAT-6 expression, both cytoplasmic and nuclear staining being observed. The level of STAT-6 expression in subjects with mild asthma (median [range] percent epithelial staining, 3.4% [0% to 16.0%]; n = 14) did not differ significantly from that in normal controls (4.7% [0.0% to 20.0%]; n = 11); however, in subjects with severe asthma, epithelial STAT-6 expression (13.7% [4.8% to 25.7%]; n = 9) was increased in comparison with subjects with mild asthma and normal controls (P < .05). RT-PCR analysis showed that epithelial STAT-6 expression was heterogeneous and comprised both full-length STAT-6 and the dominant-negative variant that lacks the SH2 domain. Treatment of primary cultures of bronchial epithelial cells with IL-4 resulted in STAT-6 phosphorylation and stimulation of IL-8 secretion; however, no difference in the responses of epithelial cells was observed between normal (n = 12) and asthmatic (n = 14) donors.

Conclusion: These data demonstrate expression and activation of STAT-6 in normal and asthmatic bronchial epithelium. The activity of this transcription factor is likely to play a key role in mediating the responses of the bronchial epithelium to T(H)2 cytokines that are characteristic of the asthmatic phenotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asthma / immunology*
  • Bronchi / cytology*
  • Cells, Cultured
  • Humans
  • Immunohistochemistry
  • Interleukin-13 / pharmacology
  • Interleukin-4 / pharmacology
  • Interleukin-8 / biosynthesis
  • Janus Kinase 1
  • Models, Biological
  • Phosphorylation
  • Protein-Tyrosine Kinases / metabolism
  • RNA, Messenger / biosynthesis
  • Respiratory Mucosa / drug effects
  • Respiratory Mucosa / immunology*
  • STAT6 Transcription Factor
  • Trans-Activators / biosynthesis*
  • Trans-Activators / genetics
  • Trans-Activators / physiology*
  • Transcription, Genetic

Substances

  • Interleukin-13
  • Interleukin-8
  • RNA, Messenger
  • STAT6 Transcription Factor
  • STAT6 protein, human
  • Trans-Activators
  • Interleukin-4
  • Protein-Tyrosine Kinases
  • JAK1 protein, human
  • Janus Kinase 1