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The elastin peptide VGVAPG increases CD4(+) T-cell IL-4 production in patients with chronic obstructive pulmonary disease
BACKGROUND: In chronic obstructive pulmonary disease (COPD), lung-infiltrating inflammatory cells secrete proteases and participate in elastin breakdown and genesis of elastin-derived peptides (EP). In the present study, we hypothesized that the pattern of T lymphocytes cytokine expression may be mo...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805078/ https://www.ncbi.nlm.nih.gov/pubmed/33435988 http://dx.doi.org/10.1186/s12931-020-01609-4 |
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author | Lemaire, Flora Audonnet, Sandra Perotin, Jeanne-Marie Gaudry, Pierre Dury, Sandra Ancel, Julien Lebargy, François Antonicelli, Frank Deslée, Gaëtan Le Naour, Richard |
author_facet | Lemaire, Flora Audonnet, Sandra Perotin, Jeanne-Marie Gaudry, Pierre Dury, Sandra Ancel, Julien Lebargy, François Antonicelli, Frank Deslée, Gaëtan Le Naour, Richard |
author_sort | Lemaire, Flora |
collection | PubMed |
description | BACKGROUND: In chronic obstructive pulmonary disease (COPD), lung-infiltrating inflammatory cells secrete proteases and participate in elastin breakdown and genesis of elastin-derived peptides (EP). In the present study, we hypothesized that the pattern of T lymphocytes cytokine expression may be modulated by EP in COPD patients. METHODS: CD4(+) and CD8(+) T-cells, sorted from peripheral blood mononuclear cells (PBMC) collected from COPD patients (n = 29) and controls (n = 13) were cultured with or without EP. Cytokine expression in T-cell phenotypes was analyzed by multicolor flow cytometry, whereas desmosine concentration, a specific marker of elastin degradation, was measured in sera. RESULTS: Compared with control, the percentage of IL-4 (Th2) producing CD4(+) T-cells was decreased in COPD patients (35.3 ± 3.4% and 26.3 ± 2.4%, respectively, p < 0.05), whereas no significant differences were found with IFN-γ (Th1) and IL-17A (Th17). Among COPD patients, two subpopulations were observed based on the percentage of IL-4 (Th2) producing CD4(+) T-cells, of which only one expressed high IL-4 levels in association with high levels of desmosine and strong smoking exposure (n = 7). Upon stimulation with VGVAPG, a bioactive EP motif, the percentage of CD4(+) T cells expressing IL-4 significantly increased in COPD patients (p < 0.05), but not in controls. The VGVAPG-induced increase in IL-4 was inhibited in the presence of analogous peptide antagonizing VGVAPG/elastin receptor (S-gal) interactions. CONCLUSIONS: The present study demonstrates that the VGVAPG elastin peptide modulates CD4(+) T-cells IL-4 production in COPD. Monitoring IL-4 in circulating CD4(+) T-cells may help to better characterize COPD phenotypes and could open a new pharmacologic opportunity through CD4(+) T-cells stimulation via the VGVAPG/S-gal receptor in order to favor an anti-inflammatory response in those COPD patients. |
format | Online Article Text |
id | pubmed-7805078 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-78050782021-01-14 The elastin peptide VGVAPG increases CD4(+) T-cell IL-4 production in patients with chronic obstructive pulmonary disease Lemaire, Flora Audonnet, Sandra Perotin, Jeanne-Marie Gaudry, Pierre Dury, Sandra Ancel, Julien Lebargy, François Antonicelli, Frank Deslée, Gaëtan Le Naour, Richard Respir Res Research BACKGROUND: In chronic obstructive pulmonary disease (COPD), lung-infiltrating inflammatory cells secrete proteases and participate in elastin breakdown and genesis of elastin-derived peptides (EP). In the present study, we hypothesized that the pattern of T lymphocytes cytokine expression may be modulated by EP in COPD patients. METHODS: CD4(+) and CD8(+) T-cells, sorted from peripheral blood mononuclear cells (PBMC) collected from COPD patients (n = 29) and controls (n = 13) were cultured with or without EP. Cytokine expression in T-cell phenotypes was analyzed by multicolor flow cytometry, whereas desmosine concentration, a specific marker of elastin degradation, was measured in sera. RESULTS: Compared with control, the percentage of IL-4 (Th2) producing CD4(+) T-cells was decreased in COPD patients (35.3 ± 3.4% and 26.3 ± 2.4%, respectively, p < 0.05), whereas no significant differences were found with IFN-γ (Th1) and IL-17A (Th17). Among COPD patients, two subpopulations were observed based on the percentage of IL-4 (Th2) producing CD4(+) T-cells, of which only one expressed high IL-4 levels in association with high levels of desmosine and strong smoking exposure (n = 7). Upon stimulation with VGVAPG, a bioactive EP motif, the percentage of CD4(+) T cells expressing IL-4 significantly increased in COPD patients (p < 0.05), but not in controls. The VGVAPG-induced increase in IL-4 was inhibited in the presence of analogous peptide antagonizing VGVAPG/elastin receptor (S-gal) interactions. CONCLUSIONS: The present study demonstrates that the VGVAPG elastin peptide modulates CD4(+) T-cells IL-4 production in COPD. Monitoring IL-4 in circulating CD4(+) T-cells may help to better characterize COPD phenotypes and could open a new pharmacologic opportunity through CD4(+) T-cells stimulation via the VGVAPG/S-gal receptor in order to favor an anti-inflammatory response in those COPD patients. BioMed Central 2021-01-13 2021 /pmc/articles/PMC7805078/ /pubmed/33435988 http://dx.doi.org/10.1186/s12931-020-01609-4 Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. 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 in a credit line to the data. |
spellingShingle | Research Lemaire, Flora Audonnet, Sandra Perotin, Jeanne-Marie Gaudry, Pierre Dury, Sandra Ancel, Julien Lebargy, François Antonicelli, Frank Deslée, Gaëtan Le Naour, Richard The elastin peptide VGVAPG increases CD4(+) T-cell IL-4 production in patients with chronic obstructive pulmonary disease |
title | The elastin peptide VGVAPG increases CD4(+) T-cell IL-4 production in patients with chronic obstructive pulmonary disease |
title_full | The elastin peptide VGVAPG increases CD4(+) T-cell IL-4 production in patients with chronic obstructive pulmonary disease |
title_fullStr | The elastin peptide VGVAPG increases CD4(+) T-cell IL-4 production in patients with chronic obstructive pulmonary disease |
title_full_unstemmed | The elastin peptide VGVAPG increases CD4(+) T-cell IL-4 production in patients with chronic obstructive pulmonary disease |
title_short | The elastin peptide VGVAPG increases CD4(+) T-cell IL-4 production in patients with chronic obstructive pulmonary disease |
title_sort | elastin peptide vgvapg increases cd4(+) t-cell il-4 production in patients with chronic obstructive pulmonary disease |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805078/ https://www.ncbi.nlm.nih.gov/pubmed/33435988 http://dx.doi.org/10.1186/s12931-020-01609-4 |
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