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Matrix Metalloproteinase 9 Production by Monocytes is Enhanced by TNF and Participates in the Pathology of Human Cutaneous Leishmaniasis

INTRODUCTION: Cutaneous leishmaniasis (CL) due to L.braziliensis infection is characterized by a strong inflammatory response with high levels of TNF and ulcer development. Less attention has been given to the role of mononuclear phagocytes to this process. Monocytes constitute a heterogeneous popul...

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Autores principales: Campos, Taís M., Passos, Sara T., Novais, Fernanda O., Beiting, Daniel P., Costa, Rúbia S., Queiroz, Adriano, Mosser, David, Scott, Phillip, Carvalho, Edgar M., Carvalho, Lucas P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4230914/
https://www.ncbi.nlm.nih.gov/pubmed/25393535
http://dx.doi.org/10.1371/journal.pntd.0003282
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author Campos, Taís M.
Passos, Sara T.
Novais, Fernanda O.
Beiting, Daniel P.
Costa, Rúbia S.
Queiroz, Adriano
Mosser, David
Scott, Phillip
Carvalho, Edgar M.
Carvalho, Lucas P.
author_facet Campos, Taís M.
Passos, Sara T.
Novais, Fernanda O.
Beiting, Daniel P.
Costa, Rúbia S.
Queiroz, Adriano
Mosser, David
Scott, Phillip
Carvalho, Edgar M.
Carvalho, Lucas P.
author_sort Campos, Taís M.
collection PubMed
description INTRODUCTION: Cutaneous leishmaniasis (CL) due to L.braziliensis infection is characterized by a strong inflammatory response with high levels of TNF and ulcer development. Less attention has been given to the role of mononuclear phagocytes to this process. Monocytes constitute a heterogeneous population subdivided into classical, intermediate and non-classical, and are known to migrate to inflammatory sites and secrete inflammatory mediators. TNF participates in the induction of matrix metalloproteinases (MMPs). MMP-9 is an enzyme that degrades basal membrane and its activity is controlled by the tissue inhibitor of metalloproteinase. METHODS: Mononuclear cells were obtained from ex-vivo labeling sub-populations of monocytes and MMP-9, and the frequency was determined by flow cytometry. Culture was performed during 72 hours, stimulating the cells with SLA, levels of MMP-9 and TIMP-1 in the supernatants were determined by ELISA. RESULTS: We observed that cells from CL lesions secrete high amounts of MMP-9 when compared to healthy subjects. Although MMP-9 was produced by monocytes, non-classical ones were the main source of this enzyme. We also observed that TNF produced in high level during CL contributes to MMP-9 production. CONCLUSIONS: These observations emphasize the role of monocytes, TNF and MMP-9 in the pathogenesis of L. braziliensis infection.
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spelling pubmed-42309142014-11-18 Matrix Metalloproteinase 9 Production by Monocytes is Enhanced by TNF and Participates in the Pathology of Human Cutaneous Leishmaniasis Campos, Taís M. Passos, Sara T. Novais, Fernanda O. Beiting, Daniel P. Costa, Rúbia S. Queiroz, Adriano Mosser, David Scott, Phillip Carvalho, Edgar M. Carvalho, Lucas P. PLoS Negl Trop Dis Research Article INTRODUCTION: Cutaneous leishmaniasis (CL) due to L.braziliensis infection is characterized by a strong inflammatory response with high levels of TNF and ulcer development. Less attention has been given to the role of mononuclear phagocytes to this process. Monocytes constitute a heterogeneous population subdivided into classical, intermediate and non-classical, and are known to migrate to inflammatory sites and secrete inflammatory mediators. TNF participates in the induction of matrix metalloproteinases (MMPs). MMP-9 is an enzyme that degrades basal membrane and its activity is controlled by the tissue inhibitor of metalloproteinase. METHODS: Mononuclear cells were obtained from ex-vivo labeling sub-populations of monocytes and MMP-9, and the frequency was determined by flow cytometry. Culture was performed during 72 hours, stimulating the cells with SLA, levels of MMP-9 and TIMP-1 in the supernatants were determined by ELISA. RESULTS: We observed that cells from CL lesions secrete high amounts of MMP-9 when compared to healthy subjects. Although MMP-9 was produced by monocytes, non-classical ones were the main source of this enzyme. We also observed that TNF produced in high level during CL contributes to MMP-9 production. CONCLUSIONS: These observations emphasize the role of monocytes, TNF and MMP-9 in the pathogenesis of L. braziliensis infection. Public Library of Science 2014-11-13 /pmc/articles/PMC4230914/ /pubmed/25393535 http://dx.doi.org/10.1371/journal.pntd.0003282 Text en © 2014 Campos et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Campos, Taís M.
Passos, Sara T.
Novais, Fernanda O.
Beiting, Daniel P.
Costa, Rúbia S.
Queiroz, Adriano
Mosser, David
Scott, Phillip
Carvalho, Edgar M.
Carvalho, Lucas P.
Matrix Metalloproteinase 9 Production by Monocytes is Enhanced by TNF and Participates in the Pathology of Human Cutaneous Leishmaniasis
title Matrix Metalloproteinase 9 Production by Monocytes is Enhanced by TNF and Participates in the Pathology of Human Cutaneous Leishmaniasis
title_full Matrix Metalloproteinase 9 Production by Monocytes is Enhanced by TNF and Participates in the Pathology of Human Cutaneous Leishmaniasis
title_fullStr Matrix Metalloproteinase 9 Production by Monocytes is Enhanced by TNF and Participates in the Pathology of Human Cutaneous Leishmaniasis
title_full_unstemmed Matrix Metalloproteinase 9 Production by Monocytes is Enhanced by TNF and Participates in the Pathology of Human Cutaneous Leishmaniasis
title_short Matrix Metalloproteinase 9 Production by Monocytes is Enhanced by TNF and Participates in the Pathology of Human Cutaneous Leishmaniasis
title_sort matrix metalloproteinase 9 production by monocytes is enhanced by tnf and participates in the pathology of human cutaneous leishmaniasis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4230914/
https://www.ncbi.nlm.nih.gov/pubmed/25393535
http://dx.doi.org/10.1371/journal.pntd.0003282
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