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TNF-induced metalloproteinase-9 production is associated with neurological manifestations in HTLV-1-infected individuals

HTLV-1-infected individuals may develop a neurologic inflammatory condition known as HTLV-1-associated myelopathy (HAM/TSP), in which the high production of TNF is observed. These patients exhibit higher proviral loads, enhanced production of proinflammatory cytokines and lymphocyte proliferation in...

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Autores principales: Guerra, Mariele, Carvalho, Natália B., Santos, Silvane, Nascimento, Mauricio T., Sá, Renata, Carvalho, Augusto M., Carvalho, Edgar M., Carvalho, Lucas P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9608347/
https://www.ncbi.nlm.nih.gov/pubmed/36311773
http://dx.doi.org/10.3389/fimmu.2022.954103
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author Guerra, Mariele
Carvalho, Natália B.
Santos, Silvane
Nascimento, Mauricio T.
Sá, Renata
Carvalho, Augusto M.
Carvalho, Edgar M.
Carvalho, Lucas P.
author_facet Guerra, Mariele
Carvalho, Natália B.
Santos, Silvane
Nascimento, Mauricio T.
Sá, Renata
Carvalho, Augusto M.
Carvalho, Edgar M.
Carvalho, Lucas P.
author_sort Guerra, Mariele
collection PubMed
description HTLV-1-infected individuals may develop a neurologic inflammatory condition known as HTLV-1-associated myelopathy (HAM/TSP), in which the high production of TNF is observed. These patients exhibit higher proviral loads, enhanced production of proinflammatory cytokines and lymphocyte proliferation in comparison to asymptomatic HTLV-1 carriers and those presenting overactive bladder (OAB-HTLV-infected). Metalloproteinases (MMPs) are known to degrade the components of the blood-brain barrier, favoring the migration of infected cells into the central nervous system. Moreover, the unbalanced production of MMPs and their inhibitors (TIMPs) has also been associated with tissue damage. The present work studied the production of MMP-9 and TIMPs in HTLV-1-infected individuals with and without neurological manifestations. HAM/TSP patients presented higher concentrations of MMP-9 in peripheral blood mononuclear cell (PBMC) culture supernatants, as well as a higher MMP-9/TIMP-3 ratio when compared to the other groups studied. MMP-9 levels positively correlated with proviral load and TNF in OAB-HTLV-infected individuals, and the in vitro neutralization of TNF significantly decreased MMP-9 levels in PBMC culture supernatants. Our findings indicate an association between MMP-9 production and the proinflammatory state associated with HTLV-1 infection, as well as HAM/TSP.
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spelling pubmed-96083472022-10-28 TNF-induced metalloproteinase-9 production is associated with neurological manifestations in HTLV-1-infected individuals Guerra, Mariele Carvalho, Natália B. Santos, Silvane Nascimento, Mauricio T. Sá, Renata Carvalho, Augusto M. Carvalho, Edgar M. Carvalho, Lucas P. Front Immunol Immunology HTLV-1-infected individuals may develop a neurologic inflammatory condition known as HTLV-1-associated myelopathy (HAM/TSP), in which the high production of TNF is observed. These patients exhibit higher proviral loads, enhanced production of proinflammatory cytokines and lymphocyte proliferation in comparison to asymptomatic HTLV-1 carriers and those presenting overactive bladder (OAB-HTLV-infected). Metalloproteinases (MMPs) are known to degrade the components of the blood-brain barrier, favoring the migration of infected cells into the central nervous system. Moreover, the unbalanced production of MMPs and their inhibitors (TIMPs) has also been associated with tissue damage. The present work studied the production of MMP-9 and TIMPs in HTLV-1-infected individuals with and without neurological manifestations. HAM/TSP patients presented higher concentrations of MMP-9 in peripheral blood mononuclear cell (PBMC) culture supernatants, as well as a higher MMP-9/TIMP-3 ratio when compared to the other groups studied. MMP-9 levels positively correlated with proviral load and TNF in OAB-HTLV-infected individuals, and the in vitro neutralization of TNF significantly decreased MMP-9 levels in PBMC culture supernatants. Our findings indicate an association between MMP-9 production and the proinflammatory state associated with HTLV-1 infection, as well as HAM/TSP. Frontiers Media S.A. 2022-10-13 /pmc/articles/PMC9608347/ /pubmed/36311773 http://dx.doi.org/10.3389/fimmu.2022.954103 Text en Copyright © 2022 Guerra, Carvalho, Santos, Nascimento, Sá, Carvalho, Carvalho and Carvalho https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Guerra, Mariele
Carvalho, Natália B.
Santos, Silvane
Nascimento, Mauricio T.
Sá, Renata
Carvalho, Augusto M.
Carvalho, Edgar M.
Carvalho, Lucas P.
TNF-induced metalloproteinase-9 production is associated with neurological manifestations in HTLV-1-infected individuals
title TNF-induced metalloproteinase-9 production is associated with neurological manifestations in HTLV-1-infected individuals
title_full TNF-induced metalloproteinase-9 production is associated with neurological manifestations in HTLV-1-infected individuals
title_fullStr TNF-induced metalloproteinase-9 production is associated with neurological manifestations in HTLV-1-infected individuals
title_full_unstemmed TNF-induced metalloproteinase-9 production is associated with neurological manifestations in HTLV-1-infected individuals
title_short TNF-induced metalloproteinase-9 production is associated with neurological manifestations in HTLV-1-infected individuals
title_sort tnf-induced metalloproteinase-9 production is associated with neurological manifestations in htlv-1-infected individuals
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9608347/
https://www.ncbi.nlm.nih.gov/pubmed/36311773
http://dx.doi.org/10.3389/fimmu.2022.954103
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