Trypanosoma cruzi: effect of the absence of 5-lipoxygenase (5-LO)-derived leukotrienes on levels of cytokines, nitric oxide and iNOS expression in cardiac tissue in the acute phase of infection in mice.
Leukotrienes are important mediators of inflammatory responses. In this study, we investigated the effect of the absence of 5-lipoxygenase (5-LO)-derived leukotrienes on levels of cytokines, nitric oxide (NO) and iNOS expression in cardiac tissue of mice infected with Trypanosoma cruzi, the agent of Chagas' disease. NO is a key mediator of parasite killing in mice experimentally infected with T. cruzi, and previous studies have suggested that leukotrienes, such as LTB(4), induces NO synthesis in T. cruzi-infected macrophages and plays a relevant role in the killing of parasite in a NO-dependent manner. We therefore investigated whether leukotrienes would have a similar role in vivo in controlling the parasite burden by regulating NO activity. We have made the striking observation that absence of 5-LO-derived leukotrienes results in increased NO and IL-6 production in the plasma with a concomitant decrease in the expression of iNOS in the cardiac tissue on day 12 after T. cruzi infection. These findings indicate that endogenous leukotrienes are important regulators of NO activity in the heart and therefore influence the cardiac parasite burden without exerting a direct action on IL-6 production in the acute phase of infection with T. cruzi.
Panis
Carolina
C
Laboratório de Imunopatologia Experimental, Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, CEP 86051-970 Londrina, Paraná, Brasil.
Mazzuco
Tânia Longo
TL
Costa
Cauê Zortéa Fernandes
CZ
Victorino
Vanessa Jacob
VJ
Tatakihara
Vera Lúcia Hideko
VL
Yamauchi
Lucy Megumi
LM
Yamada-Ogatta
Sueli Fumie
SF
Cecchini
Rubens
R
Rizzo
Luiz Vicente
LV
Pinge-Filho
Phileno
P
D000208:Acute Disease; D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics / Q000378:metabolism*; D002598:Chagas Cardiomyopathy / Q000378:metabolism*; D016207:Cytokines / Q000097:blood / Q000378:metabolism*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006321:Heart / Q000469:parasitology; D007150:Immunohistochemistry; D015289:Leukotrienes / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism; D009569:Nitric Oxide / Q000097:blood / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*
D016207:Cytokines; D015289:Leukotrienes; D009569:Nitric Oxide; D001094:Arachidonate 5-Lipoxygenase; D052247:Nitric Oxide Synthase Type II