Glucocorticoids inhibit GATA-3 phosphorylation and activity in T cells

Glucocorticoid (GC) immunosuppression and anti-inflammatory action involve the regulation of several transcription factors (TFs). GCs inhibit the acute production of T-helper (Th) 1 and Th2 cytokines but ultimately favor a shift toward Th2 phenotype. GCs inhibit the transcriptional activity of T-bet...

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Autores principales:	Liberman, Ana, Druker, Jimena Paola, Refojo, Damián
Publicado:	2009
Materias:	GCs Interleukin 5 p38 mitogen-activated protein kinase T helper 2 cyclic AMP dexamethasone glucocorticoid glucocorticoid receptor interleukin 5 messenger RNA mifepristone mitogen activated protein kinase p38 transcription factor GATA 3 transcription factor T bet animal cell article cell differentiation controlled study DNA binding genetic transcription human human cell IC 50 mouse nonhuman phenotype priority journal protein expression protein phosphorylation Th2 cell Animals Cell Line Cercopithecus aethiops COS Cells Cyclic AMP-Dependent Protein Kinases Dexamethasone GATA3 Transcription Factor Hela Cells Humans Hydrocortisone Immunoprecipitation Interleukin-5 Mice Mice, Inbred BALB C p38 Mitogen-Activated Protein Kinases Phosphorylation RNA, Messenger Signal Transduction Th2 Cells
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_08926638_v23_n5_p1558_Liberman http://hdl.handle.net/20.500.12110/paper_08926638_v23_n5_p1558_Liberman
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_08926638_v23_n5_p1558_Liberman
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spelling	paper:paper_08926638_v23_n5_p1558_Liberman2023-06-08T15:47:23Z Glucocorticoids inhibit GATA-3 phosphorylation and activity in T cells Liberman, Ana Druker, Jimena Paola Refojo, Damián GCs Interleukin 5 p38 mitogen-activated protein kinase T helper 2 cyclic AMP dexamethasone glucocorticoid glucocorticoid receptor interleukin 5 messenger RNA mifepristone mitogen activated protein kinase p38 transcription factor GATA 3 transcription factor T bet animal cell article cell differentiation controlled study DNA binding genetic transcription human human cell IC 50 mouse nonhuman phenotype priority journal protein expression protein phosphorylation Th2 cell Animals Cell Line Cercopithecus aethiops COS Cells Cyclic AMP-Dependent Protein Kinases Dexamethasone GATA3 Transcription Factor Hela Cells Humans Hydrocortisone Immunoprecipitation Interleukin-5 Mice Mice, Inbred BALB C p38 Mitogen-Activated Protein Kinases Phosphorylation RNA, Messenger Signal Transduction Th2 Cells Glucocorticoid (GC) immunosuppression and anti-inflammatory action involve the regulation of several transcription factors (TFs). GCs inhibit the acute production of T-helper (Th) 1 and Th2 cytokines but ultimately favor a shift toward Th2 phenotype. GCs inhibit the transcriptional activity of T-bet Th1 TF by a transrepression mechanism. Here we analyze GC regulation of GATA-3, the master driver of Th2 differentiation. We found that GCs inhibit GATA-3 transcriptional activity. We demonstrate that this mechanism does not involve physical interaction between the glucocorticoid receptor (GR) and GATA-3 or reduction of GATA-3 binding to DNA, as described previously for T-bet. Instead, GCs inhibit GATA-3 activity by inhibition of p38 mitogen-activated protein kinase induced GATA-3 phosphorylation. GCs also inhibit GATA-3 mRNA and protein expression. Finally, GATA-3 inhibition affects the interleukin-5 gene, a central Th2 cytokine. The IC50 of dexamethasone is 10 nM with a maximum effect at 100 nM. All inhibitory actions were blocked by the GR antagonist RU38486 (1 uM), proving the specificity of GR action. In view of the crucial role of GATA-3 in T-cell differentiation and in-flammation, we propose that the mechanism of GATA-3 inhibition compared with that in T-bet may have relevant implications in understanding and modulating the antiinflammatory and Th-regulatory properties of GCs. © FASEB. Fil:Liberman, A.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Druker, J. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Refojo, D. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2009 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_08926638_v23_n5_p1558_Liberman http://hdl.handle.net/20.500.12110/paper_08926638_v23_n5_p1558_Liberman
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	GCs Interleukin 5 p38 mitogen-activated protein kinase T helper 2 cyclic AMP dexamethasone glucocorticoid glucocorticoid receptor interleukin 5 messenger RNA mifepristone mitogen activated protein kinase p38 transcription factor GATA 3 transcription factor T bet animal cell article cell differentiation controlled study DNA binding genetic transcription human human cell IC 50 mouse nonhuman phenotype priority journal protein expression protein phosphorylation Th2 cell Animals Cell Line Cercopithecus aethiops COS Cells Cyclic AMP-Dependent Protein Kinases Dexamethasone GATA3 Transcription Factor Hela Cells Humans Hydrocortisone Immunoprecipitation Interleukin-5 Mice Mice, Inbred BALB C p38 Mitogen-Activated Protein Kinases Phosphorylation RNA, Messenger Signal Transduction Th2 Cells
spellingShingle	GCs Interleukin 5 p38 mitogen-activated protein kinase T helper 2 cyclic AMP dexamethasone glucocorticoid glucocorticoid receptor interleukin 5 messenger RNA mifepristone mitogen activated protein kinase p38 transcription factor GATA 3 transcription factor T bet animal cell article cell differentiation controlled study DNA binding genetic transcription human human cell IC 50 mouse nonhuman phenotype priority journal protein expression protein phosphorylation Th2 cell Animals Cell Line Cercopithecus aethiops COS Cells Cyclic AMP-Dependent Protein Kinases Dexamethasone GATA3 Transcription Factor Hela Cells Humans Hydrocortisone Immunoprecipitation Interleukin-5 Mice Mice, Inbred BALB C p38 Mitogen-Activated Protein Kinases Phosphorylation RNA, Messenger Signal Transduction Th2 Cells Liberman, Ana Druker, Jimena Paola Refojo, Damián Glucocorticoids inhibit GATA-3 phosphorylation and activity in T cells
topic_facet	GCs Interleukin 5 p38 mitogen-activated protein kinase T helper 2 cyclic AMP dexamethasone glucocorticoid glucocorticoid receptor interleukin 5 messenger RNA mifepristone mitogen activated protein kinase p38 transcription factor GATA 3 transcription factor T bet animal cell article cell differentiation controlled study DNA binding genetic transcription human human cell IC 50 mouse nonhuman phenotype priority journal protein expression protein phosphorylation Th2 cell Animals Cell Line Cercopithecus aethiops COS Cells Cyclic AMP-Dependent Protein Kinases Dexamethasone GATA3 Transcription Factor Hela Cells Humans Hydrocortisone Immunoprecipitation Interleukin-5 Mice Mice, Inbred BALB C p38 Mitogen-Activated Protein Kinases Phosphorylation RNA, Messenger Signal Transduction Th2 Cells
description	Glucocorticoid (GC) immunosuppression and anti-inflammatory action involve the regulation of several transcription factors (TFs). GCs inhibit the acute production of T-helper (Th) 1 and Th2 cytokines but ultimately favor a shift toward Th2 phenotype. GCs inhibit the transcriptional activity of T-bet Th1 TF by a transrepression mechanism. Here we analyze GC regulation of GATA-3, the master driver of Th2 differentiation. We found that GCs inhibit GATA-3 transcriptional activity. We demonstrate that this mechanism does not involve physical interaction between the glucocorticoid receptor (GR) and GATA-3 or reduction of GATA-3 binding to DNA, as described previously for T-bet. Instead, GCs inhibit GATA-3 activity by inhibition of p38 mitogen-activated protein kinase induced GATA-3 phosphorylation. GCs also inhibit GATA-3 mRNA and protein expression. Finally, GATA-3 inhibition affects the interleukin-5 gene, a central Th2 cytokine. The IC50 of dexamethasone is 10 nM with a maximum effect at 100 nM. All inhibitory actions were blocked by the GR antagonist RU38486 (1 uM), proving the specificity of GR action. In view of the crucial role of GATA-3 in T-cell differentiation and in-flammation, we propose that the mechanism of GATA-3 inhibition compared with that in T-bet may have relevant implications in understanding and modulating the antiinflammatory and Th-regulatory properties of GCs. © FASEB.
author	Liberman, Ana Druker, Jimena Paola Refojo, Damián
author_facet	Liberman, Ana Druker, Jimena Paola Refojo, Damián
author_sort	Liberman, Ana
title	Glucocorticoids inhibit GATA-3 phosphorylation and activity in T cells
title_short	Glucocorticoids inhibit GATA-3 phosphorylation and activity in T cells
title_full	Glucocorticoids inhibit GATA-3 phosphorylation and activity in T cells
title_fullStr	Glucocorticoids inhibit GATA-3 phosphorylation and activity in T cells
title_full_unstemmed	Glucocorticoids inhibit GATA-3 phosphorylation and activity in T cells
title_sort	glucocorticoids inhibit gata-3 phosphorylation and activity in t cells
publishDate	2009
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_08926638_v23_n5_p1558_Liberman http://hdl.handle.net/20.500.12110/paper_08926638_v23_n5_p1558_Liberman
work_keys_str_mv	AT libermanana glucocorticoidsinhibitgata3phosphorylationandactivityintcells AT drukerjimenapaola glucocorticoidsinhibitgata3phosphorylationandactivityintcells AT refojodamian glucocorticoidsinhibitgata3phosphorylationandactivityintcells
_version_	1768545012965965824

Glucocorticoids inhibit GATA-3 phosphorylation and activity in T cells

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