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.
Talvani
Andre
A
Laboratório de doença de Chagas, DECBI/NUPEB, Universidade Federal de Ouro Preto, ICEB II, Campus Morro do Cruzeiro-Bauxita, 35400-000, Ouro Preto, MG, Brazil. talvani@nupeb.ufop.br
Coutinho
Sibele Ferreira
SF
Barcelos
Luciola da Silva
Lda S
Teixeira
Mauro Martins
MM
D000818:Animals; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis*; D000242:Cyclic AMP / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006023:Glycoproteins / Q000276:immunology* / Q000302:isolation & purification; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis*; D015800:Protozoan Proteins / Q000276:immunology* / Q000302:isolation & purification; D014349:Trypanosoma cruzi / Q000737:chemistry* / Q000276:immunology
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D006023:Glycoproteins; D015800:Protozoan Proteins; D009569:Nitric Oxide; D000242:Cyclic AMP