Efeito regulador da PGE2 na produção de TNF-α e IL-17 na atividade microbicida na leishmaniose canina.
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Data
2019-08-15
Autores
Venturin, Gabriela Lovizutto
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Universidade Estadual Paulista (Unesp)
Resumo
A leishmaniose canina (CanL) é causada pelo parasito intracelular Leishmania infantum. Devido ao alto parasitismo na pele o cão é considerado o principal reservatório urbano da L. Infantum. A prostaglandina-E2 (PGE2) possui propriedades reguladoras potentes do sistema imunológico e pode se ligar aos receptores EP1, EP2 e EP4 que geram ativação celular ou EP3 que gera inibição de resposta celular. Na CanL o papel regulador da PGE2 ainda não foi estudado, por isso, os parâmetros foram avaliados em cultura de leucócitos esplênicos de cães com CanL. Avaliando o nível de PGE2, seus receptores, e seu efeito modulador sobre a PGE2 na atividade da arginase, NO2, citocinas IL-10, IL-17 e TNF-α e carga. Para isso utilizamos seus agonistas, antagonista e inibidor. Nossos resultados mostraram que a expressão do receptor EP2 diminuiu nos leucócitos esplênicos dos cães com CanL quando comparado aos cães saudáveis. Observamos que o NO2 diminuiu quando tratados com os agonistas dos receptores de PGE2 (EP1/EP2/EP3), antagonista dos receptores de PGE2 (AH-6809) e inibidor de COX-2 (NS-398). A concentração das citocinas TNF-α e a IL-17 diminuíram quando tratadas com agonista do receptor de PGE2 (EP2), e quando estimuladas com a PGE2. A carga parasitária diminuiu na cultura de leucócitos esplênicos de cães com CanL estimulados com PGE2. Concluímos que a infecção por Leishmania modula os receptores de PGE2 em cães, e que a ligação da PGE2 aos receptores pode ativar a capacidade microbicida das células.
Canine leishmaniasis (CanL) is caused by the intracellular parasite Leishmania infantum. Prostaglandin E2 (PGE2) exerts potent regulatory effects on the immune system in Leishmania infection, but in CanL has not yet been studied. In this study, PGE2 and PGE2 receptor levels and the regulatory effect of PGE2 on arginase activity; NO2; the IL-10, IL-17 and TNF-α and parasite load in the presence of agonists, antagonists and inhibitors were evaluated in cultures of splenic leukocytes obtained from dogs with CanL. Our results showed that splenic leukocytes from dogs with CanL had lower EP2 receptor levels than splenic leukocytes from healthy animals. We observed that NO2 levels decreased when the cells were treated with PGE2 receptor agonist (EP1/EP2/EP3), a PGE2 receptor antagonist (AH-6809) or a COX-2 inhibitor (NS-398) and that TNF-α and IL-17 cytokine levels decreased when the cells were treated with a PGE2 receptor agonist (EP2) or stimulated with PGE2. The parasite load in splenic leukocyte cell cultures from dogs with CanL decreased after stimulation of the cells with PGE2. We conclude that the infection of dogs by Leishmania modulates PGE2 receptors and speculate that the binding of PGE2 to its receptors may activate the microbicidal capacity of cells.
Canine leishmaniasis (CanL) is caused by the intracellular parasite Leishmania infantum. Prostaglandin E2 (PGE2) exerts potent regulatory effects on the immune system in Leishmania infection, but in CanL has not yet been studied. In this study, PGE2 and PGE2 receptor levels and the regulatory effect of PGE2 on arginase activity; NO2; the IL-10, IL-17 and TNF-α and parasite load in the presence of agonists, antagonists and inhibitors were evaluated in cultures of splenic leukocytes obtained from dogs with CanL. Our results showed that splenic leukocytes from dogs with CanL had lower EP2 receptor levels than splenic leukocytes from healthy animals. We observed that NO2 levels decreased when the cells were treated with PGE2 receptor agonist (EP1/EP2/EP3), a PGE2 receptor antagonist (AH-6809) or a COX-2 inhibitor (NS-398) and that TNF-α and IL-17 cytokine levels decreased when the cells were treated with a PGE2 receptor agonist (EP2) or stimulated with PGE2. The parasite load in splenic leukocyte cell cultures from dogs with CanL decreased after stimulation of the cells with PGE2. We conclude that the infection of dogs by Leishmania modulates PGE2 receptors and speculate that the binding of PGE2 to its receptors may activate the microbicidal capacity of cells.
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Palavras-chave
Prostaglandina, Receptores de prostaglandina, Leishmania, Cães, Prostaglandin, Receptors Prostaglandin, Dogs