Abstract
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. In 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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis / drug effects
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Apoptosis / physiology
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Cell Line
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DNA-Binding Proteins / metabolism
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Dexamethasone / pharmacology*
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Humans
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Interleukin-4 / pharmacology*
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Mammary Tumor Virus, Mouse / genetics
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Mice
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Milk Proteins*
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Promoter Regions, Genetic
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Receptors, Glucocorticoid / physiology*
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Recombinant Proteins / metabolism
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Recombinant Proteins / pharmacology
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STAT5 Transcription Factor
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STAT6 Transcription Factor
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Signal Transduction / drug effects
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Signal Transduction / physiology
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T-Lymphocytes, Cytotoxic / cytology
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T-Lymphocytes, Cytotoxic / drug effects
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T-Lymphocytes, Cytotoxic / physiology*
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Trans-Activators / genetics
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Trans-Activators / metabolism*
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Transcriptional Activation / drug effects
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Transcriptional Activation / physiology
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Transfection
Substances
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DNA-Binding Proteins
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Milk Proteins
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Receptors, Glucocorticoid
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Recombinant Proteins
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STAT5 Transcription Factor
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STAT6 Transcription Factor
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STAT6 protein, human
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Stat6 protein, mouse
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Trans-Activators
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Interleukin-4
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Dexamethasone