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

• Published in: Clinical and experimental allergy Vol. 34; no. 11; pp. 1690 - 1700
• Main Authors: Heller, N. M., Matsukura, S., Georas, S. N., Boothby, M. R., Stellato, C., Schleimer, R. P.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.11.2004; Blackwell; Wiley Subscription Services, Inc
• Subjects: airway epithelium; Allergic diseases; allergy; asthma; Biological and medical sciences; Blotting, Northern; Blotting, Western - methods; Bronchi - cytology; Bronchi - drug effects; Bronchi - metabolism; Cells, Cultured; chemokine; Chemokine CCL11; Chemokine CCL26; Chemokines, CC - biosynthesis; Chemokines, CC - genetics; eotaxin; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Expression Regulation - drug effects; glucocorticoids; Glucocorticoids - pharmacology; Humans; IL-13; IL-4; Immunopathology; Interleukin-4 - antagonists & inhibitors; Interleukin-4 - pharmacology; Medical sciences; Phosphorylation - drug effects; Recombinant Proteins - antagonists & inhibitors; Recombinant Proteins - pharmacology; RNA, Messenger - genetics; signal transduction; Signal Transduction - drug effects; STAT6; STAT6 Transcription Factor; Trans-Activators - antagonists & inhibitors; Trans-Activators - genetics; Trans-Activators - physiology; Transfection; Allergy; airway epithelium; Respiratory system; Glucocorticoid; Eotaxin; Respiratory tract; Signal transduction; Interleukin 4; Immunology; Transcription factor STAT6; Bronchus disease; STAT6; Obstructive pulmonary disease; glucocorticoids; Human; Immunopathology; Lung disease; Respiratory disease; Cytokine; IL-4; Interleukin 13; IL-13; Epithelium; Asthma; Chemokine; Epithelial cell
• ISSN: 0954-7894; 1365-2222
• DOI: 10.1111/j.1365-2222.2004.02091.x

Summary 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.