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

Authors
Journal
Journal of Allergy and Clinical Immunology
0091-6749
Publisher
Elsevier
Volume
108
Issue
5
Identifiers
DOI: 10.1067/mai.2001.119554
Keywords
  • Asthma
  • Epithelium
  • Stat-6
  • Il-4
  • Il-13
  • Th2
  • Phosphorylation
  • Il-8
Disciplines
  • Chemistry

Abstract

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 TH2 cytokines that are characteristic of the asthmatic phenotype. (J Allergy Clin Immunol 2001;108:832-8.)

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