Assessment of signal transducer and activator of transcription 6 as a target of glucocorticoid action in human airway epithelial cells

Nicola Mary Heller, S. Matsukura, S. N. Georas, M. R. Boothby, C. Stellato, Robert P. Schleimer

Research output: Contribution to journalArticle

Abstract

Background: Activation of signal transducer and activator of transcription (STAT)6 by IL-4 and IL-13 is essential in many key epithelial responses in the asthmatic airway including expression of numerous chemokines, goblet cell differentiation and mucus production and expression of other allergic inflammatory genes. While these responses are all inhibited by glucocorticoids (GC) administered systemically or by inhalation, the inhibitory mechanisms are unknown. Objective: To test the hypothesis that GC suppress allergic responses by blocking IL-4-induced STAT6 signalling in airway epithelial cells. Methods: Western blotting and reporter gene assays were used to determine whether GC could inhibit STAT6 production, phosphorylation or nuclear translocation, or whether GC could affect STAT6 transcriptional activity in the BEAS-2B airway epithelial cell line. Results: Our results showed that GC had no inhibitory effect on the total cellular or nuclear levels of STAT6 or phospho-STAT6. GC did not inhibit transcription from three different STAT6-driven reporter constructs, indicating that GC also did not inhibit STAT6 function. Conclusion: We conclude that airway epithelial STAT6 is not the central target of GC in allergic inflammation and that the inhibitory effect of GC on STAT6-mediated IL-4- and IL-13-induced responses is exerted by targeting pathways distinct from STAT6.

Original languageEnglish (US)
Pages (from-to)1690-1700
Number of pages11
JournalClinical and Experimental Allergy
Volume34
Issue number11
DOIs
StatePublished - Nov 2004

Fingerprint

STAT6 Transcription Factor
Glucocorticoids
Epithelial Cells
Interleukin-4
Interleukin-13
Goblet Cells
Mucus
Reporter Genes
Chemokines
Inhalation
Cell Differentiation
Western Blotting
Phosphorylation

Keywords

  • Airway epithelium
  • Allergy
  • Asthma
  • Chemokine
  • Eotaxin
  • Glucocorticoids
  • IL-13
  • IL-4
  • Signal transduction
  • STAT6

ASJC Scopus subject areas

  • Immunology

Cite this

Assessment of signal transducer and activator of transcription 6 as a target of glucocorticoid action in human airway epithelial cells. / Heller, Nicola Mary; Matsukura, S.; Georas, S. N.; Boothby, M. R.; Stellato, C.; Schleimer, Robert P.

In: Clinical and Experimental Allergy, Vol. 34, No. 11, 11.2004, p. 1690-1700.

Research output: Contribution to journalArticle

Heller, Nicola Mary ; Matsukura, S. ; Georas, S. N. ; Boothby, M. R. ; Stellato, C. ; Schleimer, Robert P. / Assessment of signal transducer and activator of transcription 6 as a target of glucocorticoid action in human airway epithelial cells. In: Clinical and Experimental Allergy. 2004 ; Vol. 34, No. 11. pp. 1690-1700.
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