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

Authors


and present address: Robert P. Schleimer, Northwestern University Feinberg School of Medicine, 240 E. Huron McGaw 2318, Chicago, IL 60611, USA. E-mail: rpschleimer@northwestern.edu

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.

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