The glucocorticoid receptor and STAT6 physically and functionally interact in T-lymphocytes

In lymphocytes, glucocorticoids (GC)- and interleukin-4-signaling pathways are known to interact, as evidenced by inhibition of IL-4-mediated proliferation by dexamethasone or suppression of GC-induced apoptosis by IL-4, Tn this study, we characterized the molecular basis for this reciprocal interference, We report that, in murine CTLL-2 cells, IL-4 inhibits GC-induced MMTV (mouse mammary tumor virus) promoter transactivation, and that GC suppress IL-4-induced transactivation of a STAT6 (signal transducers and activators of transcription 6)-responsive promoter without affecting IL-4-stimulated STAT6 DNA-binding. Moreover, we evidenced a physical association between GC receptor and STAT6, which proved to be functionally relevant, since STAT6 overexpression increased the IL-4 inhibitory effect on GC-induced MMTV transactivation. (C) 2000 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.