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2025-01-01
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DIFFERENCES IN THE MODULATION OF REACTIVE SPECIES, LIPID BODIES, CYCLOOXYGENASE-2, 5-LIPOXYGENASE AND PPAR-γ IN CEREBRAL MALARIA-SUSCEPTIBLE AND RESISTANT MICE
Peróxido de hidrogênio
Resposta inflamatória
Corpos lipídicos
Malaria
Óxido nítrico
PPAR-γ
Hydrogen peroxide
Inflammatory response
Lipid bodies
Malaria
Nitric oxide
PPAR-γ
Author
Affilliation
Universidade de Brasilia. Faculdade de Medicina. Laboratório de Imunologia Celular. Laboratório de Imunologia Celular. Brasilia, DF, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Laboratorio de Imunologia Molecular e Celular. Belo Horizonte, MG, Brazil
Universidade de Brasilia. Faculdade de Medicina. Laboratório de Imunologia Celular. Laboratório de Imunologia Celular. Brasilia, DF, Brazil / National Direction of Public Health. Ministry of Health of the Republic of Angola. Luanda, Angola.
Universidade de Brasília. Faculdade de Medicina. Laboratório de Patologia. Brasilia, DF, Brazil.
Universidade de Brasilia. Faculdade de Medicina. Laboratório de Imunologia Celular. Laboratório de Imunologia Celular. Brasilia, DF, Brazil.
Universidade de Brasília. Instituto de Biologia. Departamento de Biologia Celular. Laboratório de Imunologia e Inflamação. Brasilia, DF, Brazil.
Universidade de Brasilia. Faculdade de Medicina. Laboratório de Imunologia Celular. Laboratório de Imunologia Celular. Brasilia, DF, Brazil.
Fundação Oswaldo Cruz. Instituto René Rachou. Laboratorio de Imunologia Molecular e Celular. Belo Horizonte, MG, Brazil
Universidade de Brasilia. Faculdade de Medicina. Laboratório de Imunologia Celular. Laboratório de Imunologia Celular. Brasilia, DF, Brazil / National Direction of Public Health. Ministry of Health of the Republic of Angola. Luanda, Angola.
Universidade de Brasília. Faculdade de Medicina. Laboratório de Patologia. Brasilia, DF, Brazil.
Universidade de Brasilia. Faculdade de Medicina. Laboratório de Imunologia Celular. Laboratório de Imunologia Celular. Brasilia, DF, Brazil.
Universidade de Brasília. Instituto de Biologia. Departamento de Biologia Celular. Laboratório de Imunologia e Inflamação. Brasilia, DF, Brazil.
Universidade de Brasilia. Faculdade de Medicina. Laboratório de Imunologia Celular. Laboratório de Imunologia Celular. Brasilia, DF, Brazil.
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 H2O2 molecules 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 H2O2 production 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.
Keywords in Portuguese
EicosanóidesPeróxido de hidrogênio
Resposta inflamatória
Corpos lipídicos
Malaria
Óxido nítrico
PPAR-γ
Keywords
EicosanoidsHydrogen peroxide
Inflammatory response
Lipid bodies
Malaria
Nitric oxide
PPAR-γ
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