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Transforming growth factor-β increases interleukin-13 synthesis via GATA-3 transcription factor in T-lymphocytes from patients with systemic sclerosis

INTRODUCTION: Transforming growth factor (TGF)-β and interleukin (IL)-13 play a crucial role in the pathogenesis of systemic sclerosis (SSc), partly through activation of collagen production that leads to fibrosis. The aim of the present study was to determine whether TFG-β alters IL-13 production i...

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Autores principales: Baraut, Julie, Farge, Dominique, Jean-Louis, Francette, Masse, Ingrid, Grigore, Elena Ivan, Arruda, Lucas C. M., Lamartine, Jérôme, Verrecchia, Franck, Michel, Laurence
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4521372/
https://www.ncbi.nlm.nih.gov/pubmed/26227022
http://dx.doi.org/10.1186/s13075-015-0708-0
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author Baraut, Julie
Farge, Dominique
Jean-Louis, Francette
Masse, Ingrid
Grigore, Elena Ivan
Arruda, Lucas C. M.
Lamartine, Jérôme
Verrecchia, Franck
Michel, Laurence
author_facet Baraut, Julie
Farge, Dominique
Jean-Louis, Francette
Masse, Ingrid
Grigore, Elena Ivan
Arruda, Lucas C. M.
Lamartine, Jérôme
Verrecchia, Franck
Michel, Laurence
author_sort Baraut, Julie
collection PubMed
description INTRODUCTION: Transforming growth factor (TGF)-β and interleukin (IL)-13 play a crucial role in the pathogenesis of systemic sclerosis (SSc), partly through activation of collagen production that leads to fibrosis. The aim of the present study was to determine whether TFG-β alters IL-13 production in T lymphocytes from patients with SSc from that seen in those of healthy donors. METHODS: IL-13 mRNA and protein synthesis under TFG-β exposure was measured in circulating T lymphocytes from healthy donors and patients with SSc and also in the Jurkat Th2 T-cell line, using quantitative real-time PCR and fluorescence-activated cell sorting analysis, respectively. The involvement of Smad and GATA-3 transcription factors was assessed by using specific inhibitors and small interfering RNA, and the binding capacity of GATA-3 to the IL-13 gene promoter was evaluated by chromatin immunoprecipitation assay. RESULTS: TGF-β induced a significant decrease in IL-13 mRNA and protein levels in lymphocytes from healthy donors (mean [±SD] inhibition of 30 % ± 10 % and 20 % ± 7 %, respectively; p < 0.05). In contrast, TGF-β promoted a significant increase in IL-13 mRNA levels and IL-13 synthesis by CD4(+) and CD8(+) T-cell subtypes from patients with SSc, with respective increases of 2.4 ± 0.3-fold, 1.6 ± 0.05-fold and 2.7 ± 0.02-fold. The involvement of the Smad signaling pathway and upregulation of GATA-3 binding capacity on the IL-13 promoter in lymphocytes from patients with SSc contributed to the effect of TGF-β on IL-13 production. CONCLUSIONS: These results demonstrate that TGF-β upregulates IL-13 synthesis through GATA-3 expression in the T lymphocytes of patients with SSc, confirming that the GATA-3 transcription factor can be regarded as a novel therapeutic target in patients with SSc.
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spelling pubmed-45213722015-08-01 Transforming growth factor-β increases interleukin-13 synthesis via GATA-3 transcription factor in T-lymphocytes from patients with systemic sclerosis Baraut, Julie Farge, Dominique Jean-Louis, Francette Masse, Ingrid Grigore, Elena Ivan Arruda, Lucas C. M. Lamartine, Jérôme Verrecchia, Franck Michel, Laurence Arthritis Res Ther Research Article INTRODUCTION: Transforming growth factor (TGF)-β and interleukin (IL)-13 play a crucial role in the pathogenesis of systemic sclerosis (SSc), partly through activation of collagen production that leads to fibrosis. The aim of the present study was to determine whether TFG-β alters IL-13 production in T lymphocytes from patients with SSc from that seen in those of healthy donors. METHODS: IL-13 mRNA and protein synthesis under TFG-β exposure was measured in circulating T lymphocytes from healthy donors and patients with SSc and also in the Jurkat Th2 T-cell line, using quantitative real-time PCR and fluorescence-activated cell sorting analysis, respectively. The involvement of Smad and GATA-3 transcription factors was assessed by using specific inhibitors and small interfering RNA, and the binding capacity of GATA-3 to the IL-13 gene promoter was evaluated by chromatin immunoprecipitation assay. RESULTS: TGF-β induced a significant decrease in IL-13 mRNA and protein levels in lymphocytes from healthy donors (mean [±SD] inhibition of 30 % ± 10 % and 20 % ± 7 %, respectively; p < 0.05). In contrast, TGF-β promoted a significant increase in IL-13 mRNA levels and IL-13 synthesis by CD4(+) and CD8(+) T-cell subtypes from patients with SSc, with respective increases of 2.4 ± 0.3-fold, 1.6 ± 0.05-fold and 2.7 ± 0.02-fold. The involvement of the Smad signaling pathway and upregulation of GATA-3 binding capacity on the IL-13 promoter in lymphocytes from patients with SSc contributed to the effect of TGF-β on IL-13 production. CONCLUSIONS: These results demonstrate that TGF-β upregulates IL-13 synthesis through GATA-3 expression in the T lymphocytes of patients with SSc, confirming that the GATA-3 transcription factor can be regarded as a novel therapeutic target in patients with SSc. BioMed Central 2015-07-31 2015 /pmc/articles/PMC4521372/ /pubmed/26227022 http://dx.doi.org/10.1186/s13075-015-0708-0 Text en © Baraut et al. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Baraut, Julie
Farge, Dominique
Jean-Louis, Francette
Masse, Ingrid
Grigore, Elena Ivan
Arruda, Lucas C. M.
Lamartine, Jérôme
Verrecchia, Franck
Michel, Laurence
Transforming growth factor-β increases interleukin-13 synthesis via GATA-3 transcription factor in T-lymphocytes from patients with systemic sclerosis
title Transforming growth factor-β increases interleukin-13 synthesis via GATA-3 transcription factor in T-lymphocytes from patients with systemic sclerosis
title_full Transforming growth factor-β increases interleukin-13 synthesis via GATA-3 transcription factor in T-lymphocytes from patients with systemic sclerosis
title_fullStr Transforming growth factor-β increases interleukin-13 synthesis via GATA-3 transcription factor in T-lymphocytes from patients with systemic sclerosis
title_full_unstemmed Transforming growth factor-β increases interleukin-13 synthesis via GATA-3 transcription factor in T-lymphocytes from patients with systemic sclerosis
title_short Transforming growth factor-β increases interleukin-13 synthesis via GATA-3 transcription factor in T-lymphocytes from patients with systemic sclerosis
title_sort transforming growth factor-β increases interleukin-13 synthesis via gata-3 transcription factor in t-lymphocytes from patients with systemic sclerosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4521372/
https://www.ncbi.nlm.nih.gov/pubmed/26227022
http://dx.doi.org/10.1186/s13075-015-0708-0
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