Efeito in vitro da associação de CXCL10 com Glucantime® em macrófagos RAW 264.7 infectados por Leishmania infantum

Detalhes bibliográficos
Autor(a) principal: Santos, Priscilla Nascimento dos
Data de Publicação: 2018
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da Universidade Federal do Ceará (UFC)
Texto Completo: http://www.repositorio.ufc.br/handle/riufc/39764
Resumo: Visceral leishmaniasis (VL) is the gravest form of leishmaniasis caused by the genus Leishmania, and is characterized by the loss of the host's ability to generate an effective immune response. Chemokines have direct involvement in the pathogenesis of leishmaniasis, and may potentially be used as adjuvants in the treatment of such diseases. CXCL10 is a chemokine that has shown promising results in the treatment of leishmaniasis. The objective of this study was to verify the in vitro effect of the association of CXCL10 with Glucantime®on RAW 264.7 macrophages infected by L. infantum.RAW 264.7 macrophages were infected with L. infantum in vitro and treated or not with CXCL10 (25, 50 and 100 ng/ mL), Glucantime® (16 mg/mL) and CXCL10+Glucantime® (25, 50 and 100 ng/mL) + (16 mg/mL). Parasite load in infected macrophages, as well as nitric oxide (NO), IL-12, TNF-α, IL-4 and IL-10 production in the supernatants of macrophages were assessed at 24h and 48h after infection.It was observed that both CXCL10 and CXCL10 + Glucantime®, in the three concentrations used, showed a significant reduction of the parasite load in the infected macrophages, with a decrease in the concentration of 100ng/mL, 74% and 75%, respectively, and this reduction was greater than that induced by Glucantime® (50%).When the cells were treated with CXCL10 alone, the reduction in the number of intracellular parasites was correlated with the increase in NO, however, in contrast, in the association with Glucantime®, even with reduction of the parasitic load, there was a decrease in NO production, as the concentration of CXCL10 was increased.Regarding the cytokines, it was observed that CXCL10 and the association with Glucantime® induced higher concentrations of IL-12 and TNF-α, and lower IL-10 and IL-4, when compared to Glucantime®, suggesting the induction of a important profile Th1.Collectively, data from this work suggest an immunoprotective role of CXCL10, associated or not to Glucantime®, in RAW 264.7 macrophages infected by L. infantum. Data from this study may also provide information for the development of future therapeutic interventions for visceral leishmaniasis, using CXCL10 as adjuvant withGlucantime®.
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spelling Efeito in vitro da associação de CXCL10 com Glucantime® em macrófagos RAW 264.7 infectados por Leishmania infantumLeishmania infantumQuimiocina CXCL10MacrófagosCitocinasÓxido NítricoVisceral leishmaniasis (VL) is the gravest form of leishmaniasis caused by the genus Leishmania, and is characterized by the loss of the host's ability to generate an effective immune response. Chemokines have direct involvement in the pathogenesis of leishmaniasis, and may potentially be used as adjuvants in the treatment of such diseases. CXCL10 is a chemokine that has shown promising results in the treatment of leishmaniasis. The objective of this study was to verify the in vitro effect of the association of CXCL10 with Glucantime®on RAW 264.7 macrophages infected by L. infantum.RAW 264.7 macrophages were infected with L. infantum in vitro and treated or not with CXCL10 (25, 50 and 100 ng/ mL), Glucantime® (16 mg/mL) and CXCL10+Glucantime® (25, 50 and 100 ng/mL) + (16 mg/mL). Parasite load in infected macrophages, as well as nitric oxide (NO), IL-12, TNF-α, IL-4 and IL-10 production in the supernatants of macrophages were assessed at 24h and 48h after infection.It was observed that both CXCL10 and CXCL10 + Glucantime®, in the three concentrations used, showed a significant reduction of the parasite load in the infected macrophages, with a decrease in the concentration of 100ng/mL, 74% and 75%, respectively, and this reduction was greater than that induced by Glucantime® (50%).When the cells were treated with CXCL10 alone, the reduction in the number of intracellular parasites was correlated with the increase in NO, however, in contrast, in the association with Glucantime®, even with reduction of the parasitic load, there was a decrease in NO production, as the concentration of CXCL10 was increased.Regarding the cytokines, it was observed that CXCL10 and the association with Glucantime® induced higher concentrations of IL-12 and TNF-α, and lower IL-10 and IL-4, when compared to Glucantime®, suggesting the induction of a important profile Th1.Collectively, data from this work suggest an immunoprotective role of CXCL10, associated or not to Glucantime®, in RAW 264.7 macrophages infected by L. infantum. Data from this study may also provide information for the development of future therapeutic interventions for visceral leishmaniasis, using CXCL10 as adjuvant withGlucantime®.Leishmaniose visceral (LV) é a forma mais grave das leishmanioses causada por parasitos do gênero Leishmania, e tem como característica a perda da habilidade do hospedeiro em gerar uma resposta imunológica eficaz. As quimiocinas têm um envolvimento direto na patogênese das leishmanioses, e podem potencialmente serem utilizadas como adjuvantes no tratamento dessasdoenças.CXCL10 é uma quimiocina que tem mostrando resultados promissores no tratamento de leishmaniose. O objetivo deste estudo foiverificar o efeito in vitro da associação de CXCL10 com Glucantime®, em macrófagos RAW 264.7 infectados por L. infantum. Osmacrófagos foram infectados por Leishmania infantum e tratados ou não com CXCL10 (25, 50 e 100ng/mL), Glucantime® (16mg/mL)e CXCL10+Glucantime® (25, 50 e 100ng/mL) + (16mg/mL). Após 24horas e 48horas de infecção, avaliou-se a carga parasitária nos macrófagos infectados e aprodução de óxido nítrico (NO) e das citocinas IL-12, TNF-α, IL-4 e IL-10nos sobrenadantes das culturas de macrófagos.Observou-se que tanto CXCL10 como a associação CXCL10+Glucantime®, nas três concentrações utilizadas, revelaram importante redução da carga parasitária nos macrófagos infectados, com diminuição maior na concentração de 100ng/mL, 74% e 75%, respectivamente, sendo essa redução maior do que aquela induzida por Glucantime® (50%).Quando as células foram tratadas com CXCL10 sozinho, a redução do número de parasitos intracelularesestava correlacionada com o aumento de NO, entretanto, ao contrário, na associação com Glucantime®, mesmo com redução da carga parasitária, observou-se diminuição na produção de NO a medida que a concentração de CXCL10 foi aumentada. Em relação as citocinas, observou-se que CXCL10 e a associação comGlucantime®induziram maiores concentrações de IL-12 e TNF-α, e menores de IL-10 e de IL-4, quando comparado comGlucantime®, sugerindo a indução de um importante perfil Th1.Coletivamente, os dados deste trabalho sugerem um papel imunoprotetor de CXCL10, associado ou não a Glucantime®, em macrófagos RAW 264.7 infectados por L. infantum. Os dados desse estudo podem ainda fornecer informações para o desenvolvimento de futuras intervenções terapêuticas para aleishmaniose visceral, utilizando CXCL10 como adjuvante ao Glucantime®.Teixeira, Maria JaniaSantos, Priscilla Nascimento dos2019-02-19T13:07:19Z2019-02-19T13:07:19Z2018-08-10info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfSANTOS, P. N. Efeito in vitro da associação de CXCL10 com Glucantime® em macrófagos RAW 264.7 infectados por Leishmania infantum. 2018. 52 f. Dissertação (Mestrado em Patologia) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2018.http://www.repositorio.ufc.br/handle/riufc/39764porreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFCinfo:eu-repo/semantics/openAccess2022-08-19T19:54:22Zoai:repositorio.ufc.br:riufc/39764Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2024-09-11T19:02:30.360276Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.none.fl_str_mv Efeito in vitro da associação de CXCL10 com Glucantime® em macrófagos RAW 264.7 infectados por Leishmania infantum
title Efeito in vitro da associação de CXCL10 com Glucantime® em macrófagos RAW 264.7 infectados por Leishmania infantum
spellingShingle Efeito in vitro da associação de CXCL10 com Glucantime® em macrófagos RAW 264.7 infectados por Leishmania infantum
Santos, Priscilla Nascimento dos
Leishmania infantum
Quimiocina CXCL10
Macrófagos
Citocinas
Óxido Nítrico
title_short Efeito in vitro da associação de CXCL10 com Glucantime® em macrófagos RAW 264.7 infectados por Leishmania infantum
title_full Efeito in vitro da associação de CXCL10 com Glucantime® em macrófagos RAW 264.7 infectados por Leishmania infantum
title_fullStr Efeito in vitro da associação de CXCL10 com Glucantime® em macrófagos RAW 264.7 infectados por Leishmania infantum
title_full_unstemmed Efeito in vitro da associação de CXCL10 com Glucantime® em macrófagos RAW 264.7 infectados por Leishmania infantum
title_sort Efeito in vitro da associação de CXCL10 com Glucantime® em macrófagos RAW 264.7 infectados por Leishmania infantum
author Santos, Priscilla Nascimento dos
author_facet Santos, Priscilla Nascimento dos
author_role author
dc.contributor.none.fl_str_mv Teixeira, Maria Jania
dc.contributor.author.fl_str_mv Santos, Priscilla Nascimento dos
dc.subject.por.fl_str_mv Leishmania infantum
Quimiocina CXCL10
Macrófagos
Citocinas
Óxido Nítrico
topic Leishmania infantum
Quimiocina CXCL10
Macrófagos
Citocinas
Óxido Nítrico
description Visceral leishmaniasis (VL) is the gravest form of leishmaniasis caused by the genus Leishmania, and is characterized by the loss of the host's ability to generate an effective immune response. Chemokines have direct involvement in the pathogenesis of leishmaniasis, and may potentially be used as adjuvants in the treatment of such diseases. CXCL10 is a chemokine that has shown promising results in the treatment of leishmaniasis. The objective of this study was to verify the in vitro effect of the association of CXCL10 with Glucantime®on RAW 264.7 macrophages infected by L. infantum.RAW 264.7 macrophages were infected with L. infantum in vitro and treated or not with CXCL10 (25, 50 and 100 ng/ mL), Glucantime® (16 mg/mL) and CXCL10+Glucantime® (25, 50 and 100 ng/mL) + (16 mg/mL). Parasite load in infected macrophages, as well as nitric oxide (NO), IL-12, TNF-α, IL-4 and IL-10 production in the supernatants of macrophages were assessed at 24h and 48h after infection.It was observed that both CXCL10 and CXCL10 + Glucantime®, in the three concentrations used, showed a significant reduction of the parasite load in the infected macrophages, with a decrease in the concentration of 100ng/mL, 74% and 75%, respectively, and this reduction was greater than that induced by Glucantime® (50%).When the cells were treated with CXCL10 alone, the reduction in the number of intracellular parasites was correlated with the increase in NO, however, in contrast, in the association with Glucantime®, even with reduction of the parasitic load, there was a decrease in NO production, as the concentration of CXCL10 was increased.Regarding the cytokines, it was observed that CXCL10 and the association with Glucantime® induced higher concentrations of IL-12 and TNF-α, and lower IL-10 and IL-4, when compared to Glucantime®, suggesting the induction of a important profile Th1.Collectively, data from this work suggest an immunoprotective role of CXCL10, associated or not to Glucantime®, in RAW 264.7 macrophages infected by L. infantum. Data from this study may also provide information for the development of future therapeutic interventions for visceral leishmaniasis, using CXCL10 as adjuvant withGlucantime®.
publishDate 2018
dc.date.none.fl_str_mv 2018-08-10
2019-02-19T13:07:19Z
2019-02-19T13:07:19Z
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.uri.fl_str_mv SANTOS, P. N. Efeito in vitro da associação de CXCL10 com Glucantime® em macrófagos RAW 264.7 infectados por Leishmania infantum. 2018. 52 f. Dissertação (Mestrado em Patologia) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2018.
http://www.repositorio.ufc.br/handle/riufc/39764
identifier_str_mv SANTOS, P. N. Efeito in vitro da associação de CXCL10 com Glucantime® em macrófagos RAW 264.7 infectados por Leishmania infantum. 2018. 52 f. Dissertação (Mestrado em Patologia) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2018.
url http://www.repositorio.ufc.br/handle/riufc/39764
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dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
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dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositório Institucional da Universidade Federal do Ceará (UFC)
instname:Universidade Federal do Ceará (UFC)
instacron:UFC
instname_str Universidade Federal do Ceará (UFC)
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reponame_str Repositório Institucional da Universidade Federal do Ceará (UFC)
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