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

Heller NM, Matsukura S, Georas SN, Boothby MR, Stellato C, Schleimer RP
Clin Exp Allergy. 2004 34 (11): 1690-700

PMID: 15544592 · DOI:10.1111/j.1365-2222.2004.02091.x

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.

MeSH Terms (19)

Blotting, Northern Blotting, Western Bronchi Cells, Cultured Chemokine CCL11 Chemokine CCL26 Chemokines, CC Epithelial Cells Gene Expression Regulation Glucocorticoids Humans Interleukin-4 Phosphorylation Recombinant Proteins RNA, Messenger Signal Transduction STAT6 Transcription Factor Trans-Activators Transfection

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