Resistance of Leishmania (Viannia) braziliensis to nitric oxide: correlation with antimony therapy and TNF-α production
Autor(a) principal: | |
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Data de Publicação: | 2010 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFS |
Texto Completo: | https://ri.ufs.br/handle/riufs/932 |
Resumo: | BACKGROUND: Nitric oxide (NO) produced in macrophages plays a pivotal role as a leishmanicidal agent. A previous study has demonstrated that 20% of the L. (V.) braziliensis isolated from initial cutaneous lesions of patients from the endemic area of Corte de Pedra, Bahia, Brazil, were NO resistant. Additionally, 5 to 11% of the patients did not respond to three or more antimony treatments" (refractory patients). The aim of this study is to investigate if there is an association between the resistance of L. (V.) braziliensis to NO and nonresponsiveness to antimony therapy and cytokine production. METHODS: We evaluated the in vitro toxicity of NO against the promastigotes stages of L. (V.) braziliensis isolated from responsive and refractory patients, and the infectivity of the amastigote forms of these isolates against human macrophages. The supernatants from Leishmania infected macrophage were used to measure TNF-α and IL-10 levels. RESULTS: Using NaNO2 (pH 5.0) as the NO source, L. (V.) braziliensis isolated from refractory patients were more NO resistant (IC50 = 5.8 ± 4.8) than L. (V.) braziliensis isolated from responsive patients (IC50 = 2.0 ± 1.4). Four isolates were selected to infect human macrophages: NO-susceptible and NO-resistant L. (V.) braziliensis isolated from responsive and refractory patients. NO-resistant L. (V.) braziliensis isolated from refractory patients infected more macrophages stimulated with LPS and IFN-γ at 120 hours than NO-susceptible L. (V.) braziliensis isolated from refractory patients. Also, lower levels of TNF-α were detected in supernatants of macrophages infected with NO-resistant L. (V.) braziliensis as compared to macrophages infected with NO-susceptible L. (V.) braziliensis (p < 0.05 at 2, 24 and 120 hours), while no differences were detected in IL-10 levels. CONCLUSION: These data suggest that NO resistance could be related to the nonresponsiveness to antimony therapy seen in American Tegumentary Leishmaniasis. |
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Souza, AnselmoGiudice, ÂngelaPereira, Júlia M. B.Guimarães, Luiz Henrique SantosJesus, Amélia Maria Ribeiro deMoura, Tatiana Rodrigues deWilson, MaryCarvalho Filho, Edgar Marcelino deAlmeida, Roque Pacheco de2014-02-21T21:54:19Z2014-02-21T21:54:19Z2010-07SOUZA, A. Resistance of Leishmania (Viannia) braziliensis to nitric oxide: correlation with antimony therapy and TNF-α production. BMC Infectious Diseases, v. 10, n. 209, jul. 2010. Disponível em: <http://www.biomedcentral.com/1471-2334/10/209>. Acesso em: 21 fev. 2014.1471-2334https://ri.ufs.br/handle/riufs/932Creative Commons Attribution LicenseBACKGROUND: Nitric oxide (NO) produced in macrophages plays a pivotal role as a leishmanicidal agent. A previous study has demonstrated that 20% of the L. (V.) braziliensis isolated from initial cutaneous lesions of patients from the endemic area of Corte de Pedra, Bahia, Brazil, were NO resistant. Additionally, 5 to 11% of the patients did not respond to three or more antimony treatments" (refractory patients). The aim of this study is to investigate if there is an association between the resistance of L. (V.) braziliensis to NO and nonresponsiveness to antimony therapy and cytokine production. METHODS: We evaluated the in vitro toxicity of NO against the promastigotes stages of L. (V.) braziliensis isolated from responsive and refractory patients, and the infectivity of the amastigote forms of these isolates against human macrophages. The supernatants from Leishmania infected macrophage were used to measure TNF-α and IL-10 levels. RESULTS: Using NaNO2 (pH 5.0) as the NO source, L. (V.) braziliensis isolated from refractory patients were more NO resistant (IC50 = 5.8 ± 4.8) than L. (V.) braziliensis isolated from responsive patients (IC50 = 2.0 ± 1.4). Four isolates were selected to infect human macrophages: NO-susceptible and NO-resistant L. (V.) braziliensis isolated from responsive and refractory patients. NO-resistant L. (V.) braziliensis isolated from refractory patients infected more macrophages stimulated with LPS and IFN-γ at 120 hours than NO-susceptible L. (V.) braziliensis isolated from refractory patients. Also, lower levels of TNF-α were detected in supernatants of macrophages infected with NO-resistant L. (V.) braziliensis as compared to macrophages infected with NO-susceptible L. (V.) braziliensis (p < 0.05 at 2, 24 and 120 hours), while no differences were detected in IL-10 levels. CONCLUSION: These data suggest that NO resistance could be related to the nonresponsiveness to antimony therapy seen in American Tegumentary Leishmaniasis.BioMed CentralLeishmaniaLeishmania braziliensisLeishmanioseTNF-αAntimônioResistance of Leishmania (Viannia) braziliensis to nitric oxide: correlation with antimony therapy and TNF-α productioninfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleengreponame:Repositório Institucional da UFSinstname:Universidade Federal de Sergipe (UFS)instacron:UFSinfo:eu-repo/semantics/openAccessTHUMBNAILResistanceLeishmaniaBraziliensis.pdf.jpgResistanceLeishmaniaBraziliensis.pdf.jpgGenerated Thumbnailimage/jpeg1723https://ri.ufs.br/jspui/bitstream/riufs/932/4/ResistanceLeishmaniaBraziliensis.pdf.jpg772e61dca4dd07ef4813da3d7adc8e23MD54ORIGINALResistanceLeishmaniaBraziliensis.pdfResistanceLeishmaniaBraziliensis.pdfapplication/pdf786261https://ri.ufs.br/jspui/bitstream/riufs/932/1/ResistanceLeishmaniaBraziliensis.pdfc140f1510da3e071886f73a3b9b61db7MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81748https://ri.ufs.br/jspui/bitstream/riufs/932/2/license.txt8a4605be74aa9ea9d79846c1fba20a33MD52TEXTResistanceLeishmaniaBraziliensis.pdf.txtResistanceLeishmaniaBraziliensis.pdf.txtExtracted texttext/plain49629https://ri.ufs.br/jspui/bitstream/riufs/932/3/ResistanceLeishmaniaBraziliensis.pdf.txtc3b567f3a51412e3f27023cddefea273MD53riufs/9322014-09-05 20:50:34.468oai:ufs.br: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Repositório InstitucionalPUBhttps://ri.ufs.br/oai/requestrepositorio@academico.ufs.bropendoar:2014-09-05T23:50:34Repositório Institucional da UFS - Universidade Federal de Sergipe (UFS)false |
dc.title.pt_BR.fl_str_mv |
Resistance of Leishmania (Viannia) braziliensis to nitric oxide: correlation with antimony therapy and TNF-α production |
title |
Resistance of Leishmania (Viannia) braziliensis to nitric oxide: correlation with antimony therapy and TNF-α production |
spellingShingle |
Resistance of Leishmania (Viannia) braziliensis to nitric oxide: correlation with antimony therapy and TNF-α production Souza, Anselmo Leishmania Leishmania braziliensis Leishmaniose TNF-α Antimônio |
title_short |
Resistance of Leishmania (Viannia) braziliensis to nitric oxide: correlation with antimony therapy and TNF-α production |
title_full |
Resistance of Leishmania (Viannia) braziliensis to nitric oxide: correlation with antimony therapy and TNF-α production |
title_fullStr |
Resistance of Leishmania (Viannia) braziliensis to nitric oxide: correlation with antimony therapy and TNF-α production |
title_full_unstemmed |
Resistance of Leishmania (Viannia) braziliensis to nitric oxide: correlation with antimony therapy and TNF-α production |
title_sort |
Resistance of Leishmania (Viannia) braziliensis to nitric oxide: correlation with antimony therapy and TNF-α production |
author |
Souza, Anselmo |
author_facet |
Souza, Anselmo Giudice, Ângela Pereira, Júlia M. B. Guimarães, Luiz Henrique Santos Jesus, Amélia Maria Ribeiro de Moura, Tatiana Rodrigues de Wilson, Mary Carvalho Filho, Edgar Marcelino de Almeida, Roque Pacheco de |
author_role |
author |
author2 |
Giudice, Ângela Pereira, Júlia M. B. Guimarães, Luiz Henrique Santos Jesus, Amélia Maria Ribeiro de Moura, Tatiana Rodrigues de Wilson, Mary Carvalho Filho, Edgar Marcelino de Almeida, Roque Pacheco de |
author2_role |
author author author author author author author author |
dc.contributor.author.fl_str_mv |
Souza, Anselmo Giudice, Ângela Pereira, Júlia M. B. Guimarães, Luiz Henrique Santos Jesus, Amélia Maria Ribeiro de Moura, Tatiana Rodrigues de Wilson, Mary Carvalho Filho, Edgar Marcelino de Almeida, Roque Pacheco de |
dc.subject.por.fl_str_mv |
Leishmania Leishmania braziliensis Leishmaniose TNF-α Antimônio |
topic |
Leishmania Leishmania braziliensis Leishmaniose TNF-α Antimônio |
description |
BACKGROUND: Nitric oxide (NO) produced in macrophages plays a pivotal role as a leishmanicidal agent. A previous study has demonstrated that 20% of the L. (V.) braziliensis isolated from initial cutaneous lesions of patients from the endemic area of Corte de Pedra, Bahia, Brazil, were NO resistant. Additionally, 5 to 11% of the patients did not respond to three or more antimony treatments" (refractory patients). The aim of this study is to investigate if there is an association between the resistance of L. (V.) braziliensis to NO and nonresponsiveness to antimony therapy and cytokine production. METHODS: We evaluated the in vitro toxicity of NO against the promastigotes stages of L. (V.) braziliensis isolated from responsive and refractory patients, and the infectivity of the amastigote forms of these isolates against human macrophages. The supernatants from Leishmania infected macrophage were used to measure TNF-α and IL-10 levels. RESULTS: Using NaNO2 (pH 5.0) as the NO source, L. (V.) braziliensis isolated from refractory patients were more NO resistant (IC50 = 5.8 ± 4.8) than L. (V.) braziliensis isolated from responsive patients (IC50 = 2.0 ± 1.4). Four isolates were selected to infect human macrophages: NO-susceptible and NO-resistant L. (V.) braziliensis isolated from responsive and refractory patients. NO-resistant L. (V.) braziliensis isolated from refractory patients infected more macrophages stimulated with LPS and IFN-γ at 120 hours than NO-susceptible L. (V.) braziliensis isolated from refractory patients. Also, lower levels of TNF-α were detected in supernatants of macrophages infected with NO-resistant L. (V.) braziliensis as compared to macrophages infected with NO-susceptible L. (V.) braziliensis (p < 0.05 at 2, 24 and 120 hours), while no differences were detected in IL-10 levels. CONCLUSION: These data suggest that NO resistance could be related to the nonresponsiveness to antimony therapy seen in American Tegumentary Leishmaniasis. |
publishDate |
2010 |
dc.date.issued.fl_str_mv |
2010-07 |
dc.date.accessioned.fl_str_mv |
2014-02-21T21:54:19Z |
dc.date.available.fl_str_mv |
2014-02-21T21:54:19Z |
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.citation.fl_str_mv |
SOUZA, A. Resistance of Leishmania (Viannia) braziliensis to nitric oxide: correlation with antimony therapy and TNF-α production. BMC Infectious Diseases, v. 10, n. 209, jul. 2010. Disponível em: <http://www.biomedcentral.com/1471-2334/10/209>. Acesso em: 21 fev. 2014. |
dc.identifier.uri.fl_str_mv |
https://ri.ufs.br/handle/riufs/932 |
dc.identifier.issn.none.fl_str_mv |
1471-2334 |
dc.identifier.license.pt_BR.fl_str_mv |
Creative Commons Attribution License |
identifier_str_mv |
SOUZA, A. Resistance of Leishmania (Viannia) braziliensis to nitric oxide: correlation with antimony therapy and TNF-α production. BMC Infectious Diseases, v. 10, n. 209, jul. 2010. Disponível em: <http://www.biomedcentral.com/1471-2334/10/209>. Acesso em: 21 fev. 2014. 1471-2334 Creative Commons Attribution License |
url |
https://ri.ufs.br/handle/riufs/932 |
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eng |
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eng |
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BioMed Central |
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BioMed Central |
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