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Regulatory effect of PGE2 on microbicidal activity and inflammatory cytokines in canine visceral leishmaniasis

Grant number: 16/24388-6
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): March 01, 2017
Effective date (End): August 31, 2019
Field of knowledge:Agronomical Sciences - Veterinary Medicine
Principal Investigator:Valéria Marçal Felix de Lima
Grantee:Gabriela Lovizutto Venturin
Home Institution: Faculdade de Medicina Veterinária (FMVA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil

Abstract

Visceral leishmaniasis (VL) is an important disease, often fatal if left untreated. According to the Secretary of Epidemiological Surveillance of the State of São Paulo, the disease is expanding with a high mortality rate, with the city of Araçatuba concentrating the largest number of cases in the state. The dog has great epidemiological importance because it is a domestic reservoir of Leishmania spp., and the disease in dogs is more prevalent than in humans due to the lack of cellular immunity with T lymphocyte apoptosis and the production of cytokines that suppress the microbicidal function of macrophages. T cell suppression is well documented, but mechanisms that lead to failure of the immune response are poorly understood. Arginase activity is important in LV, since the increase of this enzyme can contribute to the multiplication of the parasite and to the reduction of nitric oxide (NO) synthesis, predisposing the macrophage to infection. Other factors regulating the immune response are prostaglandin E2 (PGE2), tumor necrosis factor-± (TNF-±), interleukin-10 (IL-10) and interleukin-17 (Il-17). Studies on peritoneal macrophages and splenic cells of L. donovani-infected mice show that PGE2 regulates the production of TNF-± and IL-10. The aim of this study was to evaluate the spleen adherent macrophages of dogs naturally infected with Leishmania chagasi, arginase activity, NO2 levels, PGE2, cytokines TNF-±, IL-10, IL-17 and PGE2 receptors (EP1, EP2, EP3 and EP4). An assay with the PGE2 receptor agonists will also be performed on macrophages to assess the regulatory function of PGE2 in parasite burden. In addition, healthy dog cells will be infected in vitro with Leishmania infantum and these same parameters evaluated.

Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
VENTURIN, Gabriela Lovizutto. Efeito regulador da PGE2 na produção de TNF-α e IL-17 na atividade microbicida na leishmaniose canina.. 2019. Doctoral Thesis - Universidade Estadual Paulista "Júlio de Mesquita Filho" Faculdade de Medicina Veterinária..

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