Differences in cNOS/iNOS Activity during Resistance to Trypanosoma cruzi Infection in 5-Lipoxygenase Knockout Mice

Infection with the protozoan Trypanosoma cruzi causes Chagas disease and consequently leads to severe inflammatory heart condition; however, the mechanisms driving this inflammatory response have not been completely elucidated. Nitric oxide (NO) is a key mediator of parasite killing in T. cruzi-infe...

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Main Authors: Carolina Panis, Vanessa Jacob Victorino, Vera Lúcia Hideko Tatakihara, Rubens Cecchini, Luiz Vicente Rizzo, Lucy Megumi Yamauchi, Sueli Fumie Yamada-Ogatta, Marli Cardoso Martins-Pinge, Phileno Pinge-Filho
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2019/5091630
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author Carolina Panis
Vanessa Jacob Victorino
Vera Lúcia Hideko Tatakihara
Rubens Cecchini
Luiz Vicente Rizzo
Lucy Megumi Yamauchi
Sueli Fumie Yamada-Ogatta
Marli Cardoso Martins-Pinge
Phileno Pinge-Filho
author_facet Carolina Panis
Vanessa Jacob Victorino
Vera Lúcia Hideko Tatakihara
Rubens Cecchini
Luiz Vicente Rizzo
Lucy Megumi Yamauchi
Sueli Fumie Yamada-Ogatta
Marli Cardoso Martins-Pinge
Phileno Pinge-Filho
author_sort Carolina Panis
collection DOAJ
description Infection with the protozoan Trypanosoma cruzi causes Chagas disease and consequently leads to severe inflammatory heart condition; however, the mechanisms driving this inflammatory response have not been completely elucidated. Nitric oxide (NO) is a key mediator of parasite killing in T. cruzi-infected mice, and previous studies have suggested that leukotrienes (LTs) essentially regulate the NO activity in the heart. We used infected 5-lipoxygenase-deficient mice (5-LO−/−) to explore the participation of nitric oxide synthase isoforms, inducible (iNOS) and constitutive (cNOS), in heart injury, cytokine profile, and oxidative stress during the early stage of T. cruzi infection. Our evidence suggests that the cNOS of the host is involved in the resistance of 5-LO−/− mice during T. cruzi infection. iNOS inhibition generated a remarkable increase in T. cruzi infection in the blood and heart of mice, whereas cNOS inhibition reduced cardiac parasitism (amastigote nests). Furthermore, this inhibition associates with a higher IFN-γ production and lower lipid peroxidation status. These data provide a better understanding about the influence of NO-interfering therapies for the inflammatory response toward T. cruzi infection.
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institution Kabale University
issn 0962-9351
1466-1861
language English
publishDate 2019-01-01
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series Mediators of Inflammation
spelling doaj-art-81048a03a4b84c0798e733856bde11e52025-02-03T05:53:02ZengWileyMediators of Inflammation0962-93511466-18612019-01-01201910.1155/2019/50916305091630Differences in cNOS/iNOS Activity during Resistance to Trypanosoma cruzi Infection in 5-Lipoxygenase Knockout MiceCarolina Panis0Vanessa Jacob Victorino1Vera Lúcia Hideko Tatakihara2Rubens Cecchini3Luiz Vicente Rizzo4Lucy Megumi Yamauchi5Sueli Fumie Yamada-Ogatta6Marli Cardoso Martins-Pinge7Phileno Pinge-Filho8Laboratório de Mediadores Inflamatórios, Universidade Estadual do Oeste do Paraná, Francisco Beltrão, Paraná 85605-010, BrazilLaboratório de Mediadores Inflamatórios, Universidade Estadual do Oeste do Paraná, Francisco Beltrão, Paraná 85605-010, BrazilLaboratório de Imunopatologia Experimental, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina, 86051-970 Paraná, BrazilLaboratório de Patofisiologia e Radicais Livres, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina, Paraná 86051-970, BrazilHospital Israelita Albert Einstein, Avenida Albert Einstein 627-701, Subsolo Bloco A., 05651-901 São Paulo, São Paulo, BrazilDepartamento de Microbiologia, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina, Paraná 86051-970, BrazilDepartamento de Microbiologia, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina, Paraná 86051-970, BrazilDepartamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina, Paraná 86051-970, BrazilLaboratório de Imunopatologia Experimental, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina, 86051-970 Paraná, BrazilInfection with the protozoan Trypanosoma cruzi causes Chagas disease and consequently leads to severe inflammatory heart condition; however, the mechanisms driving this inflammatory response have not been completely elucidated. Nitric oxide (NO) is a key mediator of parasite killing in T. cruzi-infected mice, and previous studies have suggested that leukotrienes (LTs) essentially regulate the NO activity in the heart. We used infected 5-lipoxygenase-deficient mice (5-LO−/−) to explore the participation of nitric oxide synthase isoforms, inducible (iNOS) and constitutive (cNOS), in heart injury, cytokine profile, and oxidative stress during the early stage of T. cruzi infection. Our evidence suggests that the cNOS of the host is involved in the resistance of 5-LO−/− mice during T. cruzi infection. iNOS inhibition generated a remarkable increase in T. cruzi infection in the blood and heart of mice, whereas cNOS inhibition reduced cardiac parasitism (amastigote nests). Furthermore, this inhibition associates with a higher IFN-γ production and lower lipid peroxidation status. These data provide a better understanding about the influence of NO-interfering therapies for the inflammatory response toward T. cruzi infection.http://dx.doi.org/10.1155/2019/5091630
spellingShingle Carolina Panis
Vanessa Jacob Victorino
Vera Lúcia Hideko Tatakihara
Rubens Cecchini
Luiz Vicente Rizzo
Lucy Megumi Yamauchi
Sueli Fumie Yamada-Ogatta
Marli Cardoso Martins-Pinge
Phileno Pinge-Filho
Differences in cNOS/iNOS Activity during Resistance to Trypanosoma cruzi Infection in 5-Lipoxygenase Knockout Mice
Mediators of Inflammation
title Differences in cNOS/iNOS Activity during Resistance to Trypanosoma cruzi Infection in 5-Lipoxygenase Knockout Mice
title_full Differences in cNOS/iNOS Activity during Resistance to Trypanosoma cruzi Infection in 5-Lipoxygenase Knockout Mice
title_fullStr Differences in cNOS/iNOS Activity during Resistance to Trypanosoma cruzi Infection in 5-Lipoxygenase Knockout Mice
title_full_unstemmed Differences in cNOS/iNOS Activity during Resistance to Trypanosoma cruzi Infection in 5-Lipoxygenase Knockout Mice
title_short Differences in cNOS/iNOS Activity during Resistance to Trypanosoma cruzi Infection in 5-Lipoxygenase Knockout Mice
title_sort differences in cnos inos activity during resistance to trypanosoma cruzi infection in 5 lipoxygenase knockout mice
url http://dx.doi.org/10.1155/2019/5091630
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