Cyclic AMP decreases the production of NO and CCL2 by macrophages stimulated with Trypanosoma cruzi GPI-mucins.

Glycosylphosphatidylinositol-anchored mucin-like glycoproteins (tGPI-mucin) present on the surface of the cellular membrane of Trypanosoma cruzi forms activate toll-like receptors 2 (TLR2) on the surface of immune cells and induce the release of several mediators of inflammation which may be relevant in the context of Chagas disease. Here, we evaluated the ability of tGPI-mucins to activate murine peritoneal macrophages to induce nitric oxide (NO) and monocyte chemoattractant protein-1 (MCP-1/CCL2). We also investigated the ability of compounds which increase or mimic cyclic adenosine monophosphate (AMP) to modulate the production of NO and CCL2. Our data show that elevation of intracellular levels of cyclic AMP prevents the release of NO and CCL2 induced by tGPI-mucins in macrophages. Overall, the release of CCL2 was decreased to a greater extent and at lower concentrations of cyclic AMP-modifying agents than the production of NO. It is suggested that the elevation of cyclic AMP during T. cruzi infection may modify the release of pro-inflammatory mediators and alter significantly the course of T. cruzi infection.