Differential Expression of Matrix Metalloproteinases 2, 9 and Cytokines by Neutrophils and Monocytes in the Clinical Forms of Chagas Disease.
Dilated cardiomyopathy, the most severe manifestation in chronic phase of Chagas disease, affects about 30% of patients and is characterized by myocardial dysfunction and interstitial fibrosis due to extracellular matrix (ECM) remodeling. ECM remodeling is regulated by proteolytic enzymes such as ma...
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doaj-c8e511cf787845b1b4c074a78672871b2020-11-24T20:44:59ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352017-01-01111e000528410.1371/journal.pntd.0005284Differential Expression of Matrix Metalloproteinases 2, 9 and Cytokines by Neutrophils and Monocytes in the Clinical Forms of Chagas Disease.Nayara I MedeirosRafaelle C G FaresEliza P FrancoGiovane R SousaRafael T MattosAna T ChavesMaria do Carmo P NunesWalderez O DutraRodrigo Correa-OliveiraManoel O C RochaJuliana A S GomesDilated cardiomyopathy, the most severe manifestation in chronic phase of Chagas disease, affects about 30% of patients and is characterized by myocardial dysfunction and interstitial fibrosis due to extracellular matrix (ECM) remodeling. ECM remodeling is regulated by proteolytic enzymes such as matrix metalloproteinases (MMPs) and cytokines produced by immune cells, including phagocytes. We evaluated by flow cytometry the expression of MMP-2, MMP-9, IL-1β, TNF-α, TGF-β and IL-10 by neutrophils and monocytes from patients with indeterminate (IND) and cardiac (CARD) clinical forms of Chagas disease and non-infected individuals (NI), before and after in vitro stimulation with Trypanosoma cruzi antigens. Our results showed an important contribution of neutrophils for MMPs production, while monocytes seemed to be involved in cytokine production. The results showed that neutrophils and monocytes from IND and CARD patients had higher intracellular levels of MMP-2 and MMP-9 than NI individuals. On the other hand, T. cruzi derived-antigens promote a differential expression of MMP-2 and MMP-9 in patients with Chagas disease and may regulate MMPs expression in neutrophils and monocytes, mainly when a cardiac alteration is not present. Our data also showed that in the presence of T. cruzi derived-antigens the production of cytokines by neutrophils and monocytes, but mainly by monocytes, may be intensified. Correlation analysis demonstrated that MMP-2 had a positive correlation with IL-10 and a negative correlation with IL-1β, whereas MMP-9 showed a negative correlation with IL-10. We also observed that IND patients presented a greater percentage of high producer cells of regulatory molecules when compared to CARD patients, indicating a different pattern in the immune response. Our data suggest that MMPs and cytokines produced by neutrophils and monocytes are important contributors for cardiac remodeling and may be an interesting target for new biomarker research.http://europepmc.org/articles/PMC5261563?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Nayara I Medeiros Rafaelle C G Fares Eliza P Franco Giovane R Sousa Rafael T Mattos Ana T Chaves Maria do Carmo P Nunes Walderez O Dutra Rodrigo Correa-Oliveira Manoel O C Rocha Juliana A S Gomes |
spellingShingle |
Nayara I Medeiros Rafaelle C G Fares Eliza P Franco Giovane R Sousa Rafael T Mattos Ana T Chaves Maria do Carmo P Nunes Walderez O Dutra Rodrigo Correa-Oliveira Manoel O C Rocha Juliana A S Gomes Differential Expression of Matrix Metalloproteinases 2, 9 and Cytokines by Neutrophils and Monocytes in the Clinical Forms of Chagas Disease. PLoS Neglected Tropical Diseases |
author_facet |
Nayara I Medeiros Rafaelle C G Fares Eliza P Franco Giovane R Sousa Rafael T Mattos Ana T Chaves Maria do Carmo P Nunes Walderez O Dutra Rodrigo Correa-Oliveira Manoel O C Rocha Juliana A S Gomes |
author_sort |
Nayara I Medeiros |
title |
Differential Expression of Matrix Metalloproteinases 2, 9 and Cytokines by Neutrophils and Monocytes in the Clinical Forms of Chagas Disease. |
title_short |
Differential Expression of Matrix Metalloproteinases 2, 9 and Cytokines by Neutrophils and Monocytes in the Clinical Forms of Chagas Disease. |
title_full |
Differential Expression of Matrix Metalloproteinases 2, 9 and Cytokines by Neutrophils and Monocytes in the Clinical Forms of Chagas Disease. |
title_fullStr |
Differential Expression of Matrix Metalloproteinases 2, 9 and Cytokines by Neutrophils and Monocytes in the Clinical Forms of Chagas Disease. |
title_full_unstemmed |
Differential Expression of Matrix Metalloproteinases 2, 9 and Cytokines by Neutrophils and Monocytes in the Clinical Forms of Chagas Disease. |
title_sort |
differential expression of matrix metalloproteinases 2, 9 and cytokines by neutrophils and monocytes in the clinical forms of chagas disease. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Neglected Tropical Diseases |
issn |
1935-2727 1935-2735 |
publishDate |
2017-01-01 |
description |
Dilated cardiomyopathy, the most severe manifestation in chronic phase of Chagas disease, affects about 30% of patients and is characterized by myocardial dysfunction and interstitial fibrosis due to extracellular matrix (ECM) remodeling. ECM remodeling is regulated by proteolytic enzymes such as matrix metalloproteinases (MMPs) and cytokines produced by immune cells, including phagocytes. We evaluated by flow cytometry the expression of MMP-2, MMP-9, IL-1β, TNF-α, TGF-β and IL-10 by neutrophils and monocytes from patients with indeterminate (IND) and cardiac (CARD) clinical forms of Chagas disease and non-infected individuals (NI), before and after in vitro stimulation with Trypanosoma cruzi antigens. Our results showed an important contribution of neutrophils for MMPs production, while monocytes seemed to be involved in cytokine production. The results showed that neutrophils and monocytes from IND and CARD patients had higher intracellular levels of MMP-2 and MMP-9 than NI individuals. On the other hand, T. cruzi derived-antigens promote a differential expression of MMP-2 and MMP-9 in patients with Chagas disease and may regulate MMPs expression in neutrophils and monocytes, mainly when a cardiac alteration is not present. Our data also showed that in the presence of T. cruzi derived-antigens the production of cytokines by neutrophils and monocytes, but mainly by monocytes, may be intensified. Correlation analysis demonstrated that MMP-2 had a positive correlation with IL-10 and a negative correlation with IL-1β, whereas MMP-9 showed a negative correlation with IL-10. We also observed that IND patients presented a greater percentage of high producer cells of regulatory molecules when compared to CARD patients, indicating a different pattern in the immune response. Our data suggest that MMPs and cytokines produced by neutrophils and monocytes are important contributors for cardiac remodeling and may be an interesting target for new biomarker research. |
url |
http://europepmc.org/articles/PMC5261563?pdf=render |
work_keys_str_mv |
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