Tumor necrosis factor, but not neutrophils, alters the metabolic profile in acute experimental arthritis
Autor(a) principal: | |
---|---|
Data de Publicação: | 2016 |
Outros Autores: | , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFMG |
Texto Completo: | http://dx.doi.org/10.1371/journal.pone.0146403 http://hdl.handle.net/1843/53841 https://orcid.org/0000-0002-7423-9802 https://orcid.org/0000-0002-5319-0210 https://orcid.org/0000-0001-8188-3738 https://orcid.org/0000-0002-7884-7709 https://orcid.org/0000-0002-4556-7671 https://orcid.org/0000-0002-1042-9762 https://orcid.org/0000-0002-5851-099X https://orcid.org/0000-0002-6944-3008 https://orcid.org/0000-0002-1695-0612 https://orcid.org/0000-0003-2256-8652 |
Resumo: | Metabolic alterations are associated with arthritis apart from obesity. However, it is still unclear which is the underlying process behind these metabolic changes. Here, we investigate the role of tumor necrosis factor (TNF) in this process in an acute model of antigen-induced arthritis (AIA). Immunized male BALB/c mice received an intra-articular injection of PBS (control) or methylated bovine serum albumin (mBSA) into their knees, and were also pre-treated with different drugs: Etanercept, an anti-TNF drug, DF2156A, a CXCR1/2 receptor antagonist, or a monoclonal antibody RB6-8C5 to deplete neutrophils. Local challenge with mBSA evoked an acute neutrophil influx into the knee joint, and enhanced the joint nociception, along with a transient systemic metabolic alteration (higher levels of glucose and lipids, and altered adipocytokines). Pre-treatment with the conventional biological Etanercept, an inhibitor of TNF action, ameliorated the nociception and the acute joint inflammation dominated by neutrophils, and markedly improved many of the altered systemic metabolites (glucose and lipids), adipocytokines and PTX3. However, the lessening of metabolic changes was not due to diminished accumulation of neutrophils in the joint by Etanercept. Reduction of neutrophil recruitment by pre-treating AIA mice with DF2156A, or even the depletion of these cells by using RB6-8C5 reduced all of the inflammatory parameters and hypernociception developed after AIA challenge, but could not prevent the metabolic changes. Therefore, the induction of joint inflammation provoked acute metabolic alterations which were involved with TNF. We suggest that the role of TNF in arthritis-associated metabolic changes is not due to local neutrophils, which are the major cells present in this model, but rather due to cytokines. |
id |
UFMG_9e7f847a376d9b08f072e14d1ff1d36d |
---|---|
oai_identifier_str |
oai:repositorio.ufmg.br:1843/53841 |
network_acronym_str |
UFMG |
network_name_str |
Repositório Institucional da UFMG |
repository_id_str |
|
spelling |
2023-05-23T21:05:38Z2023-05-23T21:05:38Z2016111http://dx.doi.org/10.1371/journal.pone.01464031932-6203http://hdl.handle.net/1843/53841https://orcid.org/0000-0002-7423-9802https://orcid.org/0000-0002-5319-0210https://orcid.org/0000-0001-8188-3738https://orcid.org/0000-0002-7884-7709https://orcid.org/0000-0002-4556-7671https://orcid.org/0000-0002-1042-9762https://orcid.org/0000-0002-5851-099Xhttps://orcid.org/0000-0002-6944-3008https://orcid.org/0000-0002-1695-0612https://orcid.org/0000-0003-2256-8652Metabolic alterations are associated with arthritis apart from obesity. However, it is still unclear which is the underlying process behind these metabolic changes. Here, we investigate the role of tumor necrosis factor (TNF) in this process in an acute model of antigen-induced arthritis (AIA). Immunized male BALB/c mice received an intra-articular injection of PBS (control) or methylated bovine serum albumin (mBSA) into their knees, and were also pre-treated with different drugs: Etanercept, an anti-TNF drug, DF2156A, a CXCR1/2 receptor antagonist, or a monoclonal antibody RB6-8C5 to deplete neutrophils. Local challenge with mBSA evoked an acute neutrophil influx into the knee joint, and enhanced the joint nociception, along with a transient systemic metabolic alteration (higher levels of glucose and lipids, and altered adipocytokines). Pre-treatment with the conventional biological Etanercept, an inhibitor of TNF action, ameliorated the nociception and the acute joint inflammation dominated by neutrophils, and markedly improved many of the altered systemic metabolites (glucose and lipids), adipocytokines and PTX3. However, the lessening of metabolic changes was not due to diminished accumulation of neutrophils in the joint by Etanercept. Reduction of neutrophil recruitment by pre-treating AIA mice with DF2156A, or even the depletion of these cells by using RB6-8C5 reduced all of the inflammatory parameters and hypernociception developed after AIA challenge, but could not prevent the metabolic changes. Therefore, the induction of joint inflammation provoked acute metabolic alterations which were involved with TNF. We suggest that the role of TNF in arthritis-associated metabolic changes is not due to local neutrophils, which are the major cells present in this model, but rather due to cytokines.porUniversidade Federal de Minas GeraisUFMGBrasilENF - DEPARTAMENTO DE NUTRIÇÃOFAR - DEPARTAMENTO DE ANÁLISES CLÍNICAS E TOXICOLÓGICASICB - DEPARTAMENTO DE BIOQUÍMICA E IMUNOLOGIAICB - DEPARTAMENTO DE FARMACOLOGIAICB - DEPARTAMENTO DE MORFOLOGIAPlos oneFatores de Necrose TumoralArtriteNeutrófilosTumor Necrosis FactorsArthritisNeutrophilsTumor necrosis factor, but not neutrophils, alters the metabolic profile in acute experimental arthritisFator de necrose tumoral, mas não neutrófilos, altera o perfil metabólico na artrite experimental agudainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttps://journals.plos.org/plosone/article?id=10.1371/journal.pone.0146403#authcontribMarina Chaves de OliveiraLuciana Padua TavaresJuliana Priscila Vago da SilvaNathália Vieira BatistaCelso Martins Queiroz JuniorAngelica Thomaz VieiraGustavo Batista de MenezesLirlândia Pires de SousaFons Van De LooMauro Martins TeixeiraFlávio Almeida AmaralAdaliene Versiani Matos Ferreiraapplication/pdfinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGLICENSELicense.txtLicense.txttext/plain; charset=utf-82042https://repositorio.ufmg.br/bitstream/1843/53841/1/License.txtfa505098d172de0bc8864fc1287ffe22MD51ORIGINALTumor Necrosis Factor, but Not Neutrophils, Alters the Metabolic Profile in Acute Experimental Arthritis.pdfTumor Necrosis Factor, but Not Neutrophils, Alters the Metabolic Profile in Acute Experimental Arthritis.pdfapplication/pdf1083820https://repositorio.ufmg.br/bitstream/1843/53841/2/Tumor%20Necrosis%20Factor%2c%20but%20Not%20Neutrophils%2c%20Alters%20the%20Metabolic%20Profile%20in%20Acute%20Experimental%20Arthritis.pdff85771e9df91000cabc787fe4b2d8b64MD521843/538412023-05-23 18:05:38.495oai:repositorio.ufmg.br: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Repositório de PublicaçõesPUBhttps://repositorio.ufmg.br/oaiopendoar:2023-05-23T21:05:38Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false |
dc.title.pt_BR.fl_str_mv |
Tumor necrosis factor, but not neutrophils, alters the metabolic profile in acute experimental arthritis |
dc.title.alternative.pt_BR.fl_str_mv |
Fator de necrose tumoral, mas não neutrófilos, altera o perfil metabólico na artrite experimental aguda |
title |
Tumor necrosis factor, but not neutrophils, alters the metabolic profile in acute experimental arthritis |
spellingShingle |
Tumor necrosis factor, but not neutrophils, alters the metabolic profile in acute experimental arthritis Marina Chaves de Oliveira Tumor Necrosis Factors Arthritis Neutrophils Fatores de Necrose Tumoral Artrite Neutrófilos |
title_short |
Tumor necrosis factor, but not neutrophils, alters the metabolic profile in acute experimental arthritis |
title_full |
Tumor necrosis factor, but not neutrophils, alters the metabolic profile in acute experimental arthritis |
title_fullStr |
Tumor necrosis factor, but not neutrophils, alters the metabolic profile in acute experimental arthritis |
title_full_unstemmed |
Tumor necrosis factor, but not neutrophils, alters the metabolic profile in acute experimental arthritis |
title_sort |
Tumor necrosis factor, but not neutrophils, alters the metabolic profile in acute experimental arthritis |
author |
Marina Chaves de Oliveira |
author_facet |
Marina Chaves de Oliveira Luciana Padua Tavares Juliana Priscila Vago da Silva Nathália Vieira Batista Celso Martins Queiroz Junior Angelica Thomaz Vieira Gustavo Batista de Menezes Lirlândia Pires de Sousa Fons Van De Loo Mauro Martins Teixeira Flávio Almeida Amaral Adaliene Versiani Matos Ferreira |
author_role |
author |
author2 |
Luciana Padua Tavares Juliana Priscila Vago da Silva Nathália Vieira Batista Celso Martins Queiroz Junior Angelica Thomaz Vieira Gustavo Batista de Menezes Lirlândia Pires de Sousa Fons Van De Loo Mauro Martins Teixeira Flávio Almeida Amaral Adaliene Versiani Matos Ferreira |
author2_role |
author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Marina Chaves de Oliveira Luciana Padua Tavares Juliana Priscila Vago da Silva Nathália Vieira Batista Celso Martins Queiroz Junior Angelica Thomaz Vieira Gustavo Batista de Menezes Lirlândia Pires de Sousa Fons Van De Loo Mauro Martins Teixeira Flávio Almeida Amaral Adaliene Versiani Matos Ferreira |
dc.subject.por.fl_str_mv |
Tumor Necrosis Factors Arthritis Neutrophils |
topic |
Tumor Necrosis Factors Arthritis Neutrophils Fatores de Necrose Tumoral Artrite Neutrófilos |
dc.subject.other.pt_BR.fl_str_mv |
Fatores de Necrose Tumoral Artrite Neutrófilos |
description |
Metabolic alterations are associated with arthritis apart from obesity. However, it is still unclear which is the underlying process behind these metabolic changes. Here, we investigate the role of tumor necrosis factor (TNF) in this process in an acute model of antigen-induced arthritis (AIA). Immunized male BALB/c mice received an intra-articular injection of PBS (control) or methylated bovine serum albumin (mBSA) into their knees, and were also pre-treated with different drugs: Etanercept, an anti-TNF drug, DF2156A, a CXCR1/2 receptor antagonist, or a monoclonal antibody RB6-8C5 to deplete neutrophils. Local challenge with mBSA evoked an acute neutrophil influx into the knee joint, and enhanced the joint nociception, along with a transient systemic metabolic alteration (higher levels of glucose and lipids, and altered adipocytokines). Pre-treatment with the conventional biological Etanercept, an inhibitor of TNF action, ameliorated the nociception and the acute joint inflammation dominated by neutrophils, and markedly improved many of the altered systemic metabolites (glucose and lipids), adipocytokines and PTX3. However, the lessening of metabolic changes was not due to diminished accumulation of neutrophils in the joint by Etanercept. Reduction of neutrophil recruitment by pre-treating AIA mice with DF2156A, or even the depletion of these cells by using RB6-8C5 reduced all of the inflammatory parameters and hypernociception developed after AIA challenge, but could not prevent the metabolic changes. Therefore, the induction of joint inflammation provoked acute metabolic alterations which were involved with TNF. We suggest that the role of TNF in arthritis-associated metabolic changes is not due to local neutrophils, which are the major cells present in this model, but rather due to cytokines. |
publishDate |
2016 |
dc.date.issued.fl_str_mv |
2016 |
dc.date.accessioned.fl_str_mv |
2023-05-23T21:05:38Z |
dc.date.available.fl_str_mv |
2023-05-23T21:05:38Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1843/53841 |
dc.identifier.doi.pt_BR.fl_str_mv |
http://dx.doi.org/10.1371/journal.pone.0146403 |
dc.identifier.issn.pt_BR.fl_str_mv |
1932-6203 |
dc.identifier.orcid.pt_BR.fl_str_mv |
https://orcid.org/0000-0002-7423-9802 https://orcid.org/0000-0002-5319-0210 https://orcid.org/0000-0001-8188-3738 https://orcid.org/0000-0002-7884-7709 https://orcid.org/0000-0002-4556-7671 https://orcid.org/0000-0002-1042-9762 https://orcid.org/0000-0002-5851-099X https://orcid.org/0000-0002-6944-3008 https://orcid.org/0000-0002-1695-0612 https://orcid.org/0000-0003-2256-8652 |
url |
http://dx.doi.org/10.1371/journal.pone.0146403 http://hdl.handle.net/1843/53841 https://orcid.org/0000-0002-7423-9802 https://orcid.org/0000-0002-5319-0210 https://orcid.org/0000-0001-8188-3738 https://orcid.org/0000-0002-7884-7709 https://orcid.org/0000-0002-4556-7671 https://orcid.org/0000-0002-1042-9762 https://orcid.org/0000-0002-5851-099X https://orcid.org/0000-0002-6944-3008 https://orcid.org/0000-0002-1695-0612 https://orcid.org/0000-0003-2256-8652 |
identifier_str_mv |
1932-6203 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.ispartof.pt_BR.fl_str_mv |
Plos one |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Minas Gerais |
dc.publisher.initials.fl_str_mv |
UFMG |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
ENF - DEPARTAMENTO DE NUTRIÇÃO FAR - DEPARTAMENTO DE ANÁLISES CLÍNICAS E TOXICOLÓGICAS ICB - DEPARTAMENTO DE BIOQUÍMICA E IMUNOLOGIA ICB - DEPARTAMENTO DE FARMACOLOGIA ICB - DEPARTAMENTO DE MORFOLOGIA |
publisher.none.fl_str_mv |
Universidade Federal de Minas Gerais |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UFMG instname:Universidade Federal de Minas Gerais (UFMG) instacron:UFMG |
instname_str |
Universidade Federal de Minas Gerais (UFMG) |
instacron_str |
UFMG |
institution |
UFMG |
reponame_str |
Repositório Institucional da UFMG |
collection |
Repositório Institucional da UFMG |
bitstream.url.fl_str_mv |
https://repositorio.ufmg.br/bitstream/1843/53841/1/License.txt https://repositorio.ufmg.br/bitstream/1843/53841/2/Tumor%20Necrosis%20Factor%2c%20but%20Not%20Neutrophils%2c%20Alters%20the%20Metabolic%20Profile%20in%20Acute%20Experimental%20Arthritis.pdf |
bitstream.checksum.fl_str_mv |
fa505098d172de0bc8864fc1287ffe22 f85771e9df91000cabc787fe4b2d8b64 |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 |
repository.name.fl_str_mv |
Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG) |
repository.mail.fl_str_mv |
|
_version_ |
1801676744310128640 |