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

Mullings, Rebecca E., Wilson, Susan J., Puddicombe, Sarah M., Lordan, James L., Bucchieri, Fabio, Djukanovic´, Ratko, Howarth, Peter H., Harper, Steven, Holgate, Stephen T. and Davies, Donna E. (2001) Signal transducer and activator of transcription 6 (STAT-6) expression and function in asthmatic bronchial epithelium. Journal of Allergy and Clinical Immunology, 108 (5), 832-838. (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 TH2 cytokines that are characteristic of the asthmatic phenotype.

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Contributors

Author: Susan J. Wilson

Author: Ratko Djukanovic´

Author: Donna E. Davies

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