Investigação do perfil de macrófagos M1 e M2 e de citocinas em modelos experimentais da doença pulmonar obstrutiva crônica
Autor(a) principal: | |
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Data de Publicação: | 2019 |
Outros Autores: | |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da UERJ |
Texto Completo: | http://www.bdtd.uerj.br/handle/1/17639 |
Resumo: | Alveolar macrophages are differentiated from circulating monocytes and play a central role in the pathophysiology of chronic obstructive pulmonary disease (COPD) and are a major target for thepapy. In this study, we investigated the profile of M1 and M2 macrophages and cytokines in experimental models of COPD. First, we evaluated the effect of cigarette smoke (CS) in monocytes from blood and bone marrow and lung macrophages in mice. In addition, we investigated the profile of human macrophages after exposure to a cigarette smoke extract (CSE) and we also analyzed, in COPD patients, the profile of blood monocytes. Male mice (C57BL/6, n = 54) were divided in groups: control and exposed to 12 Marlboro cigarettes (CS 5 days, CS14 days and CS 30 days). Human peripheral blood monocytes were obtained for centrifugation by a Ficoll gradient and differentiated into macrophages after incubation with GM-CSF for 7 days. Monocytes from patients with COPD and controls were also obtained from centrifugation by a Ficoll gradient. The exposure to CS for 5 days induced a pronounced influx of neutrophils and macrophages in the lung associated with increased levels of keratinocyte chemoattractant (KC), tumor necrosis factor-α (TNF-α), nitric oxide (NO), and metalloproteinase from the matrix (MMP) -12. After 14 days of exposure to CS, neutrophil recruitment and cytokine production were reduced. After 30 days of exposure to CS, there was an increase in the recruitment of alveolar macrophages and transforming growth factor- β (TGF-β) production. CS also increased the Ly6Clow monocytes in both bone marrow and blood. Human macrophages derived from monocytes (MDM) were exposed to CSE at different concentrations (2% to 10%) alone or associated with LPS (0.1μg/mL) and IL-4 (10 ng/mL) for 24 hours and cytokine profile was evaluated by ELISA. CSE increased the IL-8/CXCL8 release in a dose-dependent manner, but only CSE 4% was able to increase the MDC/CCL22 release and MMP-12 expression. The challenge with CSE 4% and LPS increased the IL-8/CXCL8 production when compared to LPS only however, IL-6 and Gro -α/CXCL1 release were significantly reduced. We observed lower in macrophages stimulated with LPS. Pretreatment of MDM with JAK 2 inhibitor tyrphostin AG 490 (25 g/mL) for 1 hour decreased the IL-8/CXCL8 production induced by CSE 4%. We confirmed the results obtained in vitro and in vivo models with data obtained from monocytes from COPD patients. We observed a greater number of intermediate monocytes in COPD patients when compared to healthy donors, associated with a lower release of Gro-α/CXCL1 and a greater release of TARC/CCL17 and MDC/CCL22, however, a lower release of IL-8/CXCL8 was observed in COPD patients. Our results showed that, initially, CS induces a pro-inflammatory response marked by M1 cytokine production, however, the chronic exposure to CS favors the M2 cytokine production, inducing a profile e "like" M2 of the macrophages. |
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Pôrto, Luis Cristovão de Moraes Sobrinohttp://lattes.cnpq.br/8153025668900773Costa, Andréa Monte Altohttp://lattes.cnpq.br/2742511199834466Martins, Mariana Renovatohttp://lattes.cnpq.br/./4873004948911165http://lattes.cnpq.br\1358855320310572Meira, Camila Oliveira da Silvacamilavs162@hotmail.com2022-04-28T13:35:19Z2019-02-19MEIRA, Camila Oliveira da Silva. Investigação do perfil de macrófagos M1 e M2 e de citocinas em modelos experimentais da doença pulmonar obstrutiva crônica. 2019. 105 f. Dissertação (Mestrado em Biociências) - Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2019 .http://www.bdtd.uerj.br/handle/1/17639Alveolar macrophages are differentiated from circulating monocytes and play a central role in the pathophysiology of chronic obstructive pulmonary disease (COPD) and are a major target for thepapy. In this study, we investigated the profile of M1 and M2 macrophages and cytokines in experimental models of COPD. First, we evaluated the effect of cigarette smoke (CS) in monocytes from blood and bone marrow and lung macrophages in mice. In addition, we investigated the profile of human macrophages after exposure to a cigarette smoke extract (CSE) and we also analyzed, in COPD patients, the profile of blood monocytes. Male mice (C57BL/6, n = 54) were divided in groups: control and exposed to 12 Marlboro cigarettes (CS 5 days, CS14 days and CS 30 days). Human peripheral blood monocytes were obtained for centrifugation by a Ficoll gradient and differentiated into macrophages after incubation with GM-CSF for 7 days. Monocytes from patients with COPD and controls were also obtained from centrifugation by a Ficoll gradient. The exposure to CS for 5 days induced a pronounced influx of neutrophils and macrophages in the lung associated with increased levels of keratinocyte chemoattractant (KC), tumor necrosis factor-α (TNF-α), nitric oxide (NO), and metalloproteinase from the matrix (MMP) -12. After 14 days of exposure to CS, neutrophil recruitment and cytokine production were reduced. After 30 days of exposure to CS, there was an increase in the recruitment of alveolar macrophages and transforming growth factor- β (TGF-β) production. CS also increased the Ly6Clow monocytes in both bone marrow and blood. Human macrophages derived from monocytes (MDM) were exposed to CSE at different concentrations (2% to 10%) alone or associated with LPS (0.1μg/mL) and IL-4 (10 ng/mL) for 24 hours and cytokine profile was evaluated by ELISA. CSE increased the IL-8/CXCL8 release in a dose-dependent manner, but only CSE 4% was able to increase the MDC/CCL22 release and MMP-12 expression. The challenge with CSE 4% and LPS increased the IL-8/CXCL8 production when compared to LPS only however, IL-6 and Gro -α/CXCL1 release were significantly reduced. We observed lower in macrophages stimulated with LPS. Pretreatment of MDM with JAK 2 inhibitor tyrphostin AG 490 (25 g/mL) for 1 hour decreased the IL-8/CXCL8 production induced by CSE 4%. We confirmed the results obtained in vitro and in vivo models with data obtained from monocytes from COPD patients. We observed a greater number of intermediate monocytes in COPD patients when compared to healthy donors, associated with a lower release of Gro-α/CXCL1 and a greater release of TARC/CCL17 and MDC/CCL22, however, a lower release of IL-8/CXCL8 was observed in COPD patients. Our results showed that, initially, CS induces a pro-inflammatory response marked by M1 cytokine production, however, the chronic exposure to CS favors the M2 cytokine production, inducing a profile e "like" M2 of the macrophages.Os macrófagos alveolares se diferenciam à partir de monócitos circulantes e desempenham um papel central na patogênese da doença pulmonar obstrutiva crônica (DPOC), sendo apontados como alvos terapêuticos. O objetivo deste estudo foi investigar o perfil de macrófagos M1 e M2 e de citocinas em modelos experimentais de DPOC. Para alcançar tal objetivo, nós avaliamos o efeito da fumaça do cigarro (FC) em monócitos da medula óssea e circulantes e em macrófagos pulmonares de camundongos. Além disso, investigamos o perfil de macrófagos humanos após a exposição ao extrato da fumaça do cigarro (EFC) e analisamos o perfil de monócitos de pacientes com DPOC. Camundongos machos (C57BL/6, n = 54) foram expostos a 12 cigarros Marlboro por 5, 14 e 30 dias. Os monócitos do sangue periférico humano foram obtidos a partir da centrifugação por um gradiente de ficoll e diferenciados em macrófagos após a incubação com GM-CSF por sete dias. Os monócitos dos pacientes com DPOC e controles também foram obtidos a partir da centrifugação por um gradiente de ficoll. Camundongos expostos à FC por 5 dias aumentaram o número de neutrófilos e macrófagos no pulmão, associado a níveis aumentados da quimiocina derivada de queratinócitos (KC), fator de necrose tumoral-α (TNF-α), óxido nítrico (NO) e metaloproteinase de matriz (MMP) -12. Após 14 dias de exposição à FC, o recrutamento de neutrófilos e produção de citocinas foram reduzidos e, após30 dias de exposição à FC, houve um aumento no número de macrófagos alveolares e maior liberação do fator de transformação do crescimento-β (TGF-β). A FC induziu um aumento de monócitos Ly6Clow tanto na medula óssea, quanto na circulação. Os macrófagos humanos derivados de monócitos (MDM) foram expostos ao EFC em diferentes concentrações (2% a 10 %) isoladamente ou associados ao LPS (0,1 μg/mL) e ou (IL-4 10 ng/mL) durante 24h. Em seguida, o perfil de citocinas foi avaliado por ELISA. A exposição ao EFC aumentou a liberação de IL-8/CXCL8 de modo dose-dependente, mas apenas o EFC a 4% foi capaz de aumentar a liberação de MDC/CCL22 e a expressão de MMP-12. A associação do EFC 4% ao LPS aumento a liberação de IL-8/CXCL8 e reduziu a produção de IL-6 e Gro-α/CXCL1 nos macrófagos, quando comparado ao grupo LPS. Avaliamos também, o envolvimento da Janus kinase 2 (JAK) na produção de IL-8/CXCL8 induzida pelo EFC 4%. Nossos resultados mostraram que o inibidor da JAK 2 (tyrphostin AG 490) diminuiu a liberação de IL-8/CXCL8 induzida pelo EFC 4%. A partir dos resultados obtidos nos modelos in vitro e in vivo, utilizamos monócitos de pacientes com DPOC para confirmação dos dados. Observamos um aumento no número monócitos intermediários, uma maior liberação de TARC/CCL17 e MDC/CCL22 e, uma diminuição na produção de IL-8/CXCL8 e Gro-α/CXCL1 em pacientes com DPOC quando comparados a doadores saudáveis. A partir dos resultados obtidos, afirmamos que, inicialmente, a FC induz uma resposta pró-inflamatória contudo, ao longo da exposição, a FC é capaz de alterar o perfil de citocinas secretadas, favorecendo um perfil semelhante ao de macrófagos M2Submitted by Heloísa CB/A (helobdtd@gmail.com) on 2022-04-28T13:35:19Z No. of bitstreams: 1 Camila Oliveira da Silva Meira.pdf: 11422636 bytes, checksum: 73f715c098dcf1a887c9375d1909b8ff (MD5)Made available in DSpace on 2022-04-28T13:35:19Z (GMT). No. of bitstreams: 1 Camila Oliveira da Silva Meira.pdf: 11422636 bytes, checksum: 73f715c098dcf1a887c9375d1909b8ff (MD5) Previous issue date: 2019-02-19Conselho Nacional de Desenvolvimento Científico e Tecnológico - CNPqapplication/pdfporUniversidade do Estado do Rio de JaneiroPrograma de Pós-Graduação em BiociênciasUERJBrasilCentro Biomédico::Instituto de Biologia Roberto Alcantara GomesDoença pulmonar obstrutiva crônicaPulmões - Doenças obstrutivasMonócitosCitocinasMacrófagosCIENCIAS BIOLOGICAS::BIOLOGIA GERALInvestigação do perfil de macrófagos M1 e M2 e de citocinas em modelos experimentais da doença pulmonar obstrutiva crônicaInvestigation of the profile of macrophages M1 and M2 and cytokines in experimental models of chronic obstructive pulmonary diseaseinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UERJinstname:Universidade do Estado do Rio de Janeiro (UERJ)instacron:UERJORIGINALDissertação - Camila Oliveira da Silva Meira - 2019 - Completa.pdfDissertação - Camila Oliveira da Silva Meira - 2019 - Completa.pdfapplication/pdf11422636http://www.bdtd.uerj.br/bitstream/1/17639/2/Disserta%C3%A7%C3%A3o+-+Camila+Oliveira+da+Silva+Meira+-+2019+-+Completa.pdf73f715c098dcf1a887c9375d1909b8ffMD52LICENSElicense.txtlicense.txttext/plain; charset=utf-82123http://www.bdtd.uerj.br/bitstream/1/17639/1/license.txte5502652da718045d7fcd832b79fca29MD511/176392024-02-26 11:39:29.48oai:www.bdtd.uerj.br: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Biblioteca Digital de Teses e Dissertaçõeshttp://www.bdtd.uerj.br/PUBhttps://www.bdtd.uerj.br:8443/oai/requestbdtd.suporte@uerj.bropendoar:29032024-02-26T14:39:29Biblioteca Digital de Teses e Dissertações da UERJ - Universidade do Estado do Rio de Janeiro (UERJ)false |
dc.title.por.fl_str_mv |
Investigação do perfil de macrófagos M1 e M2 e de citocinas em modelos experimentais da doença pulmonar obstrutiva crônica |
dc.title.alternative.eng.fl_str_mv |
Investigation of the profile of macrophages M1 and M2 and cytokines in experimental models of chronic obstructive pulmonary disease |
title |
Investigação do perfil de macrófagos M1 e M2 e de citocinas em modelos experimentais da doença pulmonar obstrutiva crônica |
spellingShingle |
Investigação do perfil de macrófagos M1 e M2 e de citocinas em modelos experimentais da doença pulmonar obstrutiva crônica Meira, Camila Oliveira da Silva Doença pulmonar obstrutiva crônica Pulmões - Doenças obstrutivas Monócitos Citocinas Macrófagos CIENCIAS BIOLOGICAS::BIOLOGIA GERAL |
title_short |
Investigação do perfil de macrófagos M1 e M2 e de citocinas em modelos experimentais da doença pulmonar obstrutiva crônica |
title_full |
Investigação do perfil de macrófagos M1 e M2 e de citocinas em modelos experimentais da doença pulmonar obstrutiva crônica |
title_fullStr |
Investigação do perfil de macrófagos M1 e M2 e de citocinas em modelos experimentais da doença pulmonar obstrutiva crônica |
title_full_unstemmed |
Investigação do perfil de macrófagos M1 e M2 e de citocinas em modelos experimentais da doença pulmonar obstrutiva crônica |
title_sort |
Investigação do perfil de macrófagos M1 e M2 e de citocinas em modelos experimentais da doença pulmonar obstrutiva crônica |
author |
Meira, Camila Oliveira da Silva |
author_facet |
Meira, Camila Oliveira da Silva camilavs162@hotmail.com |
author_role |
author |
author2 |
camilavs162@hotmail.com |
author2_role |
author |
dc.contributor.advisor1.fl_str_mv |
Pôrto, Luis Cristovão de Moraes Sobrino |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/8153025668900773 |
dc.contributor.referee1.fl_str_mv |
Costa, Andréa Monte Alto |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/2742511199834466 |
dc.contributor.referee2.fl_str_mv |
Martins, Mariana Renovato |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/./4873004948911165 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br\1358855320310572 |
dc.contributor.author.fl_str_mv |
Meira, Camila Oliveira da Silva camilavs162@hotmail.com |
contributor_str_mv |
Pôrto, Luis Cristovão de Moraes Sobrino Costa, Andréa Monte Alto Martins, Mariana Renovato |
dc.subject.por.fl_str_mv |
Doença pulmonar obstrutiva crônica Pulmões - Doenças obstrutivas Monócitos Citocinas Macrófagos |
topic |
Doença pulmonar obstrutiva crônica Pulmões - Doenças obstrutivas Monócitos Citocinas Macrófagos CIENCIAS BIOLOGICAS::BIOLOGIA GERAL |
dc.subject.cnpq.fl_str_mv |
CIENCIAS BIOLOGICAS::BIOLOGIA GERAL |
description |
Alveolar macrophages are differentiated from circulating monocytes and play a central role in the pathophysiology of chronic obstructive pulmonary disease (COPD) and are a major target for thepapy. In this study, we investigated the profile of M1 and M2 macrophages and cytokines in experimental models of COPD. First, we evaluated the effect of cigarette smoke (CS) in monocytes from blood and bone marrow and lung macrophages in mice. In addition, we investigated the profile of human macrophages after exposure to a cigarette smoke extract (CSE) and we also analyzed, in COPD patients, the profile of blood monocytes. Male mice (C57BL/6, n = 54) were divided in groups: control and exposed to 12 Marlboro cigarettes (CS 5 days, CS14 days and CS 30 days). Human peripheral blood monocytes were obtained for centrifugation by a Ficoll gradient and differentiated into macrophages after incubation with GM-CSF for 7 days. Monocytes from patients with COPD and controls were also obtained from centrifugation by a Ficoll gradient. The exposure to CS for 5 days induced a pronounced influx of neutrophils and macrophages in the lung associated with increased levels of keratinocyte chemoattractant (KC), tumor necrosis factor-α (TNF-α), nitric oxide (NO), and metalloproteinase from the matrix (MMP) -12. After 14 days of exposure to CS, neutrophil recruitment and cytokine production were reduced. After 30 days of exposure to CS, there was an increase in the recruitment of alveolar macrophages and transforming growth factor- β (TGF-β) production. CS also increased the Ly6Clow monocytes in both bone marrow and blood. Human macrophages derived from monocytes (MDM) were exposed to CSE at different concentrations (2% to 10%) alone or associated with LPS (0.1μg/mL) and IL-4 (10 ng/mL) for 24 hours and cytokine profile was evaluated by ELISA. CSE increased the IL-8/CXCL8 release in a dose-dependent manner, but only CSE 4% was able to increase the MDC/CCL22 release and MMP-12 expression. The challenge with CSE 4% and LPS increased the IL-8/CXCL8 production when compared to LPS only however, IL-6 and Gro -α/CXCL1 release were significantly reduced. We observed lower in macrophages stimulated with LPS. Pretreatment of MDM with JAK 2 inhibitor tyrphostin AG 490 (25 g/mL) for 1 hour decreased the IL-8/CXCL8 production induced by CSE 4%. We confirmed the results obtained in vitro and in vivo models with data obtained from monocytes from COPD patients. We observed a greater number of intermediate monocytes in COPD patients when compared to healthy donors, associated with a lower release of Gro-α/CXCL1 and a greater release of TARC/CCL17 and MDC/CCL22, however, a lower release of IL-8/CXCL8 was observed in COPD patients. Our results showed that, initially, CS induces a pro-inflammatory response marked by M1 cytokine production, however, the chronic exposure to CS favors the M2 cytokine production, inducing a profile e "like" M2 of the macrophages. |
publishDate |
2019 |
dc.date.issued.fl_str_mv |
2019-02-19 |
dc.date.accessioned.fl_str_mv |
2022-04-28T13:35:19Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
MEIRA, Camila Oliveira da Silva. Investigação do perfil de macrófagos M1 e M2 e de citocinas em modelos experimentais da doença pulmonar obstrutiva crônica. 2019. 105 f. Dissertação (Mestrado em Biociências) - Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2019 . |
dc.identifier.uri.fl_str_mv |
http://www.bdtd.uerj.br/handle/1/17639 |
identifier_str_mv |
MEIRA, Camila Oliveira da Silva. Investigação do perfil de macrófagos M1 e M2 e de citocinas em modelos experimentais da doença pulmonar obstrutiva crônica. 2019. 105 f. Dissertação (Mestrado em Biociências) - Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, 2019 . |
url |
http://www.bdtd.uerj.br/handle/1/17639 |
dc.language.iso.fl_str_mv |
por |
language |
por |
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 do Estado do Rio de Janeiro |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Biociências |
dc.publisher.initials.fl_str_mv |
UERJ |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
Centro Biomédico::Instituto de Biologia Roberto Alcantara Gomes |
publisher.none.fl_str_mv |
Universidade do Estado do Rio de Janeiro |
dc.source.none.fl_str_mv |
reponame:Biblioteca Digital de Teses e Dissertações da UERJ instname:Universidade do Estado do Rio de Janeiro (UERJ) instacron:UERJ |
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Universidade do Estado do Rio de Janeiro (UERJ) |
instacron_str |
UERJ |
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UERJ |
reponame_str |
Biblioteca Digital de Teses e Dissertações da UERJ |
collection |
Biblioteca Digital de Teses e Dissertações da UERJ |
bitstream.url.fl_str_mv |
http://www.bdtd.uerj.br/bitstream/1/17639/2/Disserta%C3%A7%C3%A3o+-+Camila+Oliveira+da+Silva+Meira+-+2019+-+Completa.pdf http://www.bdtd.uerj.br/bitstream/1/17639/1/license.txt |
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73f715c098dcf1a887c9375d1909b8ff e5502652da718045d7fcd832b79fca29 |
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MD5 MD5 |
repository.name.fl_str_mv |
Biblioteca Digital de Teses e Dissertações da UERJ - Universidade do Estado do Rio de Janeiro (UERJ) |
repository.mail.fl_str_mv |
bdtd.suporte@uerj.br |
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1792352358179536896 |