title: Differences in the modulation of reactive species, lipid bodies, cyclooxygenase-2, 5-lipoxygenase and PPAR-γ in cerebral malaria-susceptible and resistant mice.
abstract: Proinflammatory responses are associated with the severity of cerebral malaria. NO, H2O2, eicosanoid and PPAR-γ are involved in proinflammatory responses, but regulation of these factors is unclear in malaria. This work aimed to compare the expression of eicosanoid-forming-enzymes in cerebral malaria-susceptible CBA and C57BL/6 and -resistant BALB/c mice. Mice were infected with Plasmodium berghei ANKA, and the survival rates and parasitemia curves were assessed. On the sixth day post-infection, cyclooxygenase-2 and 5-lipoxygenase in brain sections were assessed by immunohistochemistry, and, NO, H2O2, lipid bodies, and PPAR-γ expression were assessed in peritoneal macrophages. The C57BL/6 had more severe disease with a lower survival time, higher parasitemia and lower production of plasmodicidal NO and H2O2molecules than BALB/c. Enhanced COX-2 and 5-LOX expression were observed in brain tissue cells and vessels from C57BL/6 mice, and these mice expressed higher constitutive PPAR-γ levels. There was no translocation of PPAR-γ from cytoplasm to nucleus in macrophages from these mice. CBA mice had enhanced COX-2 expression in brain tissue cells and vessels and also lacked PPAR-γ cytoplasm-to-nucleus translocation. The resistant BALB/c mice presented higher survival time, lower parasitemia and higher NO and H2O2production on the sixth day post-infection. These mice did not express either COX-2 or 5-LOX in brain tissue cells and vessels. Our data showed that besides the high parasite burden and lack of microbicidal molecules, an imbalance with high COX-2 and 5-LOX eicosanoid expression and a lack of regulatory PPAR-γ cytoplasm-to-nucleus translocation in macrophages were observed in mice that develop cerebral malaria.
authors.affiliation: Laboratory of Cellular Immunology, Pathology, Faculty of Medicine, University of Brasilia, Campus Darcy Ribeiro, Brasilia, Distrito Federal 70.910.900, Brazil.
authors.forename: Tatiana K S
authors.initials: TK
authors.lastname: Borges
authors.affiliation: Laboratory of Cellular Immunology, Pathology, Faculty of Medicine, University of Brasilia, Campus Darcy Ribeiro, Brasilia, Distrito Federal 70.910.900, Brazil; Laboratory of Cellular and Molecular Immunology, René Rachou Research Center, Belo Horizonte, Minas Gerais 30.190.002 Brazil.
authors.forename: Érica A R
authors.initials: ÉA
authors.lastname: Alves
authors.affiliation: Laboratory of Cellular Immunology, Pathology, Faculty of Medicine, University of Brasilia, Campus Darcy Ribeiro, Brasilia, Distrito Federal 70.910.900, Brazil; National Direction of Public Health, Ministry of Health of the Republic of Angola, Luanda, Angola.
authors.forename: Henda A R
authors.initials: HA
authors.lastname: Vasconcelos
authors.affiliation: Laboratory of Pathology, Pathology, Faculty of Medicine, University of Brasilia, Campus Darcy Ribeiro, Brasilia, Distrito Federal 70.910.900, Brazil.
authors.forename: Fabiana P
authors.initials: FP
authors.lastname: Carneiro
authors.affiliation: Laboratory of Cellular Immunology, Pathology, Faculty of Medicine, University of Brasilia, Campus Darcy Ribeiro, Brasilia, Distrito Federal 70.910.900, Brazil.
authors.forename: André M
authors.initials: AM
authors.lastname: Nicola
authors.affiliation: Laboratory of Immunology and Inflammation, Department of Cellular Biology, Biology Institute, University of Brasilia, Campus Darcy Ribeiro, Brasilia, Distrito Federal 70.910.900, Brazil.
authors.forename: Kelly G
authors.initials: KG
authors.lastname: Magalhães
authors.affiliation: Laboratory of Cellular Immunology, Pathology, Faculty of Medicine, University of Brasilia, Campus Darcy Ribeiro, Brasilia, Distrito Federal 70.910.900, Brazil. Electronic address: mimjunqueira@unb.br.
authors.forename: Maria Imaculada
authors.initials: MI
authors.lastname: Muniz-Junqueira
mesh_terms: D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D004198:Disease Susceptibility; D015870:Gene Expression; D066292:Lipid Droplets / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000378:metabolism; D016779:Malaria, Cerebral / Q000378:metabolism* / Q000401:mortality / Q000469:parasitology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D017628:Microglia / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism*; D010962:Plasmodium berghei; D021381:Protein Transport; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D009573:Nitrites; D047495:PPAR gamma; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D001094:Arachidonate 5-Lipoxygenase; D051546:Cyclooxygenase 2
keywords: Eicosanoids; Hydrogen peroxide; Inflammatory response; Lipid bodies; Malaria; Nitric oxide; PPAR-γ