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Mechanism of action of lipoxin in the protection against experimental cerebral malaria

Grant number: 16/12855-9
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): October 01, 2016
Status:Discontinued
Field of knowledge:Biological Sciences - Parasitology
Principal Investigator:Fabio Trindade Maranhão Costa
Grantee:João Luiz da Silva Filho
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated scholarship(s):19/01578-2 - Host-parasite interactions in the bone marrow: a key role in malaria pathogenesis, BE.EP.PD

Abstract

Malaria is the most widespread parasitic disease, and despite the many efforts made to eradicate malaria, it accounts for more than half million deaths per year because the host-parasite interactions are not completely understood yet. Cerebral malaria (CM) is a severe neurological complication of infection with Plasmodium falciparum. Even after the appropriate antimalarial treatment, fatality rates range from 10 to 20% which highlights the importance of understanding the pathogenesis of this disease and of implementing new, rapidly acting interventions in combination with anti-plasmodium treatment. Although, cerebral malaria pathogenesis is complex and incompletely understood, observations from animal models and P. falciparum-infected humans support a hypothesis that it involves sequestration of parasitized erythrocytes and leukocytes by the brain microvasculature, and production of pro-inflammatory cytokines, such as IFN-³, TNF-, lymphotoxin-± e IL-12. However, the use of single knockout mutants for several pro-inflammatory cytokines have failed to show an obvious influence on cerebral malaria pathogenesis, suggesting that redundancy among those mediators. Previous results demonstrate that lipoxins, a class of anti-inflammatory lipid mediator derived from lipoxygenase-mediated metabolism of arachidonic acid, limit host damage during experimental cerebral malaria (ECM). In addition, animals treated with lipoxin showed prolonged survival and diminished brain inflammation. Thus, in the search for efficient therapies against CM and a better undertanding of the disease pathogenesis, the aim of this project is to elucidate the mechanisms involved in the lipoxin-induced CM protection and to determine its potential use, as adjuvant therapy, in association with antimalarials to treat severe malaria. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
BITTENCOURT, NAJARA C.; LEITE, JULIANA A.; SILVA, ANA BEATRIZ I. E.; PIMENTA, TAMIRYS S.; SILVA-FILHO, JOAO LUIZ; CASSIANO, GUSTAVO C.; LOPES, STEFANIE C. P.; DOS-SANTOS, JOAO C. K.; BOURGARD, CATARINA; NAKAYA, HELDER I.; REVOREDO DA SILVA VENTURA, ANA MARIA; LACERDA, MARCUS V. G.; FERREIRA, MARCELO U.; MACHADO, RICARDO L. D.; ALBRECHT, LETUSA; COSTA, FABIO T. M. Genetic sequence characterization and naturally acquired immune response to Plasmodium vivax Rhoptry Neck Protein 2 (PvRON2). Malaria Journal, v. 17, OCT 31 2018. Web of Science Citations: 0.
BASTOS, MARCELE F.; KAYANO, ANA CAROLINA A. V.; SILVA-FILHO, JOAO LUIZ; DOS-SANTOS, JOAO CONRADO K.; JUDICE, CARLA; BLANCO, YARA C.; SHRYOCK, NATHANIEL; SERCUNDES, MICHELLE K.; ORTOLAN, LUANA S.; FRANCELIN, CAROLINA; LEITE, JULIANA A.; OLIVEIRA, RAFAELLA; ELIAS, ROSA M.; CAMARA, NIELS O. S.; LOPES, STEFANIE C. P.; ALBRECHT, LETUSA; FARIAS, ALESSANDRO S.; VICENTE, CRISTINA P.; WERNECK, CLAUDIO C.; GIORGIO, SELMA; VERINAUD, LIANA; EPIPHANIO, SABRINA; MARINHO, CLAUDIO R. F.; LALWANI, PRITESH; AMINO, ROGERIO; ALIBERTI, JULIO; COSTA, FABIO T. M. Inhibition of hypoxia-associated response and kynurenine production in response to hyperbaric oxygen as mechanisms involved in protection against experimental cerebral malaria. FASEB JOURNAL, v. 32, n. 8, p. 4470-4481, AUG 2018. Web of Science Citations: 1.
PADUA, TATIANA A.; TORRES, NATALIA D.; CANDEA, ANDRE L. P.; SOUZA COSTA, MARIA FERNANDA; SILVA, JOHNATAS D.; SILVA-FILHO, JOAO LUIZ; COSTA, FABIO T. M.; ROCCO, PATRICIA R. M.; SOUZA, MARIANA C.; HENRIQUES, MARIA G. Therapeutic effect of Lipoxin A(4)in malaria-induced acute lung injury. Journal of Leukocyte Biology, v. 103, n. 4, p. 657-670, APR 2018. Web of Science Citations: 2.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.