PGE2 regulatory effect on TNF-α and IL-17 production on microbicidal activity in canine leishmaniasis.

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. (AU)