The glucocorticoid receptor and STAT6 physically and functionally interactin T-lymphocytes

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