Crotoxin stimulates an M1 activation profile in murine macrophages during Leishmania amazonensis infection
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Digital do Instituto Evandro Chagas (Patuá) |
Texto Completo: | https://patua.iec.gov.br/handle/iec/2855 |
Resumo: | American tegumentary leishmaniasis is caused by different species of Leishmania. This protozoan employs several mechanisms to subvert the microbicidal activity of macrophages and, given the limited efficacy of current therapies, the development of alternative treatments is essential. Animal venoms are known to exhibit a variety of pharmacological activities, including antiparasitic effects. Crotoxin (CTX) is the main component of Crotalus durissus terrificus venom, and it has several biological effects. Nevertheless, there is no report of CTX activity during macrophage - Leishmania interactions. Thus, the main objective of this study was to evaluate whether CTX has a role in macrophage M1 polarization during Leishmania infection murine macrophages, Leishmania amazonensis promastigotes and L. amazonensis-infected macrophages were challenged with CTX. MTT [3-(4,5dimethylthiazol-2-yl)-2,5-diphenyl tetrasodium bromide] toxicity assays were performed on murine macrophages, and no damage was observed in these cells. Promastigotes, however, were affected by treatment with CTX (IC50 = 22·86 µg mL-1) as were intracellular amastigotes. Macrophages treated with CTX also demonstrated increased reactive oxygen species production. After they were infected with Leishmania, macrophages exhibited an increase in nitric oxide production that converged into an M1 activation profile, as suggested by their elevated production of the cytokines interleukin-6 and tumour necrosis factor-α and changes in their morphology. CTX was able to reverse the L. amazonensis-mediated inhibition of macrophage immune responses and is capable of polarizing macrophages to the M1 profile, which is associated with a better prognosis for cutaneous leishmaniasis treatment. |
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Farias, Luis Henrique SeabraRodrigues, Ana Paula DrummondCoêlho, E. CSantos, M. FSampaio, S. CSilva, E. O2017-11-17T17:37:31Z2017-11-17T17:37:31Z2017FARIAS, Luis Henrique Seabra et al. Crotoxin stimulates an M1 activation profile in murine macrophages during Leishmania amazonensis infection. Parasitology, v. 144, n. 11, p. 1458-1467, Sept. 2017. DOI: https://doi.org/10.1017/S00311820170009440031-1820https://patua.iec.gov.br/handle/iec/285510.1017/S0031182017000944American tegumentary leishmaniasis is caused by different species of Leishmania. This protozoan employs several mechanisms to subvert the microbicidal activity of macrophages and, given the limited efficacy of current therapies, the development of alternative treatments is essential. Animal venoms are known to exhibit a variety of pharmacological activities, including antiparasitic effects. Crotoxin (CTX) is the main component of Crotalus durissus terrificus venom, and it has several biological effects. Nevertheless, there is no report of CTX activity during macrophage - Leishmania interactions. Thus, the main objective of this study was to evaluate whether CTX has a role in macrophage M1 polarization during Leishmania infection murine macrophages, Leishmania amazonensis promastigotes and L. amazonensis-infected macrophages were challenged with CTX. MTT [3-(4,5dimethylthiazol-2-yl)-2,5-diphenyl tetrasodium bromide] toxicity assays were performed on murine macrophages, and no damage was observed in these cells. Promastigotes, however, were affected by treatment with CTX (IC50 = 22·86 µg mL-1) as were intracellular amastigotes. Macrophages treated with CTX also demonstrated increased reactive oxygen species production. After they were infected with Leishmania, macrophages exhibited an increase in nitric oxide production that converged into an M1 activation profile, as suggested by their elevated production of the cytokines interleukin-6 and tumour necrosis factor-α and changes in their morphology. CTX was able to reverse the L. amazonensis-mediated inhibition of macrophage immune responses and is capable of polarizing macrophages to the M1 profile, which is associated with a better prognosis for cutaneous leishmaniasis treatment.Federal University of Para. Institute of Biological Sciences. Laboratory of Parasitology and Laboratory of Structural Biology. Belém, PA, Brazil / National Institute of Science and Technology in Structural Biology and Bioimaging. Rio de Janeiro, RJ, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil / National Institute of Science and Technology in Structural Biology and Bioimaging. Rio de Janeiro, RJ, Brazil.Federal University of Para. Institute of Biological Sciences. Laboratory of Parasitology and Laboratory of Structural Biology. Belém, PA, Brazil.University of São Paulo. Department,Institute of Biomedical Sciences. Cell and Developmental Biology. São Paulo, SP, Brazil.Butantan Institute. Laboratory of Pathophysiology. São Paulo, SP, Brazil / University of São Paulo. Institute of Biomedical Sciences. Department of Pharmacology. São Paulo, SP, Brazil.Federal University of Para. Institute of Biological Sciences. Laboratory of Parasitology and Laboratory of Structural Biology. Belém, PA, Brazil / National Institute of Science and Technology in Structural Biology and Bioimaging. Rio de Janeiro, RJ, Brazil.engCambridge University PressCrotoxin stimulates an M1 activation profile in murine macrophages during Leishmania amazonensis infectioninfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleLeishmania / efeitos de drogasLeishmaniose Cutânea / farmacologiaCrotoxina / efeitos adversosCrotoxina / farmacologiaCrotoxina / toxicidadeCrotoxina / uso terapêuticoMacrófagos Peritoneais / imunologiaMacrófagos Peritoneais / efeitos de drogasÓxido Nítrico / metabolismoEspécies Reativas de Oxigênio / metabolismoAtivação de Macrófagos / efeitos de drogasFator Estimulador de Colônias de Macrófagos / efeitos de drogasCitometria de Fluxo / métodosCamundongos Endogâmicos BALB Cinfo:eu-repo/semantics/embargoedAccessreponame:Repositório Digital do Instituto Evandro Chagas (Patuá)instname:Instituto Evandro Chagas (IEC)instacron:IECLICENSElicense.txtlicense.txttext/plain; charset=utf-871https://patua.iec.gov.br/bitstreams/bd68235c-f858-4c89-839a-2533465b2e5b/download52f1732ea66fbd1123abe39f5373b797MD52TEXTCrotoxin stimulates an M1 activation profile in murine macrophages during Leishmania amazonensis infection.pdf.txtCrotoxin stimulates an M1 activation profile in murine macrophages during Leishmania amazonensis infection.pdf.txtExtracted texttext/plain2https://patua.iec.gov.br/bitstreams/ed29956f-c56d-4a43-9def-4ec363acc2f4/downloade1c06d85ae7b8b032bef47e42e4c08f9MD57THUMBNAILCrotoxin stimulates an M1 activation profile in murine macrophages during Leishmania amazonensis infection.pdf.jpgCrotoxin stimulates an M1 activation profile in murine macrophages during Leishmania amazonensis infection.pdf.jpgGenerated Thumbnailimage/jpeg3095https://patua.iec.gov.br/bitstreams/67fbcb9e-48a1-4812-9814-d4884b1b664b/download71859d578212107f7f8c49a4ce09d9eeMD58ORIGINALCrotoxin stimulates an M1 activation profile in murine macrophages during Leishmania amazonensis infection.pdfCrotoxin stimulates an M1 activation profile in murine macrophages during Leishmania amazonensis infection.pdfapplication/pdf551083https://patua.iec.gov.br/bitstreams/09d108a4-fdee-49a4-9877-b15e6d3dc652/downloadc9a9c128e29cac82a5d7fdf3f4e6da73MD56iec/28552023-06-13 14:15:00.082oai:patua.iec.gov.br:iec/2855https://patua.iec.gov.brRepositório InstitucionalPUBhttps://patua.iec.gov.br/oai/requestclariceneta@iec.gov.br || Biblioteca@iec.gov.bropendoar:2023-06-13T14:15Repositório Digital do Instituto Evandro Chagas (Patuá) - Instituto Evandro Chagas (IEC)falseVG9kb3Mgb3MgZG9jdW1lbnRvcyBkZXNzYSBjb2xlw6fDo28gc2VndWVtIGEgTGljZW7Dp2EgQ3JlYXRpdmUgY29tbW9ucy4= |
dc.title.pt_BR.fl_str_mv |
Crotoxin stimulates an M1 activation profile in murine macrophages during Leishmania amazonensis infection |
title |
Crotoxin stimulates an M1 activation profile in murine macrophages during Leishmania amazonensis infection |
spellingShingle |
Crotoxin stimulates an M1 activation profile in murine macrophages during Leishmania amazonensis infection Farias, Luis Henrique Seabra Leishmania / efeitos de drogas Leishmaniose Cutânea / farmacologia Crotoxina / efeitos adversos Crotoxina / farmacologia Crotoxina / toxicidade Crotoxina / uso terapêutico Macrófagos Peritoneais / imunologia Macrófagos Peritoneais / efeitos de drogas Óxido Nítrico / metabolismo Espécies Reativas de Oxigênio / metabolismo Ativação de Macrófagos / efeitos de drogas Fator Estimulador de Colônias de Macrófagos / efeitos de drogas Citometria de Fluxo / métodos Camundongos Endogâmicos BALB C |
title_short |
Crotoxin stimulates an M1 activation profile in murine macrophages during Leishmania amazonensis infection |
title_full |
Crotoxin stimulates an M1 activation profile in murine macrophages during Leishmania amazonensis infection |
title_fullStr |
Crotoxin stimulates an M1 activation profile in murine macrophages during Leishmania amazonensis infection |
title_full_unstemmed |
Crotoxin stimulates an M1 activation profile in murine macrophages during Leishmania amazonensis infection |
title_sort |
Crotoxin stimulates an M1 activation profile in murine macrophages during Leishmania amazonensis infection |
author |
Farias, Luis Henrique Seabra |
author_facet |
Farias, Luis Henrique Seabra Rodrigues, Ana Paula Drummond Coêlho, E. C Santos, M. F Sampaio, S. C Silva, E. O |
author_role |
author |
author2 |
Rodrigues, Ana Paula Drummond Coêlho, E. C Santos, M. F Sampaio, S. C Silva, E. O |
author2_role |
author author author author author |
dc.contributor.author.fl_str_mv |
Farias, Luis Henrique Seabra Rodrigues, Ana Paula Drummond Coêlho, E. C Santos, M. F Sampaio, S. C Silva, E. O |
dc.subject.decsPrimary.pt_BR.fl_str_mv |
Leishmania / efeitos de drogas Leishmaniose Cutânea / farmacologia Crotoxina / efeitos adversos Crotoxina / farmacologia Crotoxina / toxicidade Crotoxina / uso terapêutico Macrófagos Peritoneais / imunologia Macrófagos Peritoneais / efeitos de drogas Óxido Nítrico / metabolismo Espécies Reativas de Oxigênio / metabolismo Ativação de Macrófagos / efeitos de drogas Fator Estimulador de Colônias de Macrófagos / efeitos de drogas Citometria de Fluxo / métodos Camundongos Endogâmicos BALB C |
topic |
Leishmania / efeitos de drogas Leishmaniose Cutânea / farmacologia Crotoxina / efeitos adversos Crotoxina / farmacologia Crotoxina / toxicidade Crotoxina / uso terapêutico Macrófagos Peritoneais / imunologia Macrófagos Peritoneais / efeitos de drogas Óxido Nítrico / metabolismo Espécies Reativas de Oxigênio / metabolismo Ativação de Macrófagos / efeitos de drogas Fator Estimulador de Colônias de Macrófagos / efeitos de drogas Citometria de Fluxo / métodos Camundongos Endogâmicos BALB C |
description |
American tegumentary leishmaniasis is caused by different species of Leishmania. This protozoan employs several mechanisms to subvert the microbicidal activity of macrophages and, given the limited efficacy of current therapies, the development of alternative treatments is essential. Animal venoms are known to exhibit a variety of pharmacological activities, including antiparasitic effects. Crotoxin (CTX) is the main component of Crotalus durissus terrificus venom, and it has several biological effects. Nevertheless, there is no report of CTX activity during macrophage - Leishmania interactions. Thus, the main objective of this study was to evaluate whether CTX has a role in macrophage M1 polarization during Leishmania infection murine macrophages, Leishmania amazonensis promastigotes and L. amazonensis-infected macrophages were challenged with CTX. MTT [3-(4,5dimethylthiazol-2-yl)-2,5-diphenyl tetrasodium bromide] toxicity assays were performed on murine macrophages, and no damage was observed in these cells. Promastigotes, however, were affected by treatment with CTX (IC50 = 22·86 µg mL-1) as were intracellular amastigotes. Macrophages treated with CTX also demonstrated increased reactive oxygen species production. After they were infected with Leishmania, macrophages exhibited an increase in nitric oxide production that converged into an M1 activation profile, as suggested by their elevated production of the cytokines interleukin-6 and tumour necrosis factor-α and changes in their morphology. CTX was able to reverse the L. amazonensis-mediated inhibition of macrophage immune responses and is capable of polarizing macrophages to the M1 profile, which is associated with a better prognosis for cutaneous leishmaniasis treatment. |
publishDate |
2017 |
dc.date.accessioned.fl_str_mv |
2017-11-17T17:37:31Z |
dc.date.available.fl_str_mv |
2017-11-17T17:37:31Z |
dc.date.issued.fl_str_mv |
2017 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
FARIAS, Luis Henrique Seabra et al. Crotoxin stimulates an M1 activation profile in murine macrophages during Leishmania amazonensis infection. Parasitology, v. 144, n. 11, p. 1458-1467, Sept. 2017. DOI: https://doi.org/10.1017/S0031182017000944 |
dc.identifier.uri.fl_str_mv |
https://patua.iec.gov.br/handle/iec/2855 |
dc.identifier.issn.-.fl_str_mv |
0031-1820 |
dc.identifier.doi.-.fl_str_mv |
10.1017/S0031182017000944 |
identifier_str_mv |
FARIAS, Luis Henrique Seabra et al. Crotoxin stimulates an M1 activation profile in murine macrophages during Leishmania amazonensis infection. Parasitology, v. 144, n. 11, p. 1458-1467, Sept. 2017. DOI: https://doi.org/10.1017/S0031182017000944 0031-1820 10.1017/S0031182017000944 |
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Cambridge University Press |
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Cambridge University Press |
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