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

Abstract

Canine leishmaniasis (CanL) is caused by the intracellular parasite Leishmania infantum. Prostaglandin E2 (PGE₂ ) exerts potent regulatory effects on the immune system in experimental model Leishmania infection, but this influence has not yet been studied in CanL. In this study, PGE₂ and PGE₂ receptor levels and the regulatory effect of PGE₂ on arginase activity, NO₂ , IL-10, IL-17, IFN-γ, TNF-α and parasite load were evaluated in cultures of splenic leucocytes obtained from dogs with CanL in the presence of agonists and inhibitors. Our results showed that splenic leucocytes from dogs with CanL had lower EP2 receptor levels than those of splenic leucocytes from healthy animals. We observed that NO₂ levels decreased when the cells were treated with a PGE₂ receptor agonist (EP1/EP2/EP3) or COX-2 inhibitor (NS-398) and that TNF-α, IL-17 and IFN-γ cytokine levels decreased when the cells were treated with a PGE₂ receptor agonist (EP2) or PGE₂ itself. The parasite load in splenic leucocyte cell cultures from dogs with CanL decreased after stimulation of the cells with PGE₂ . We conclude that Leishmania infection of dogs modulates PGE₂ receptors and speculate that the binding of PGE₂ to its receptors may activate the microbicidal capacity of cells.

Keywords: Leishmania spp.; dogs; prostaglandin E2; receptors.