Cruzipain and SP600125 induce p38 activation, alter NO/arginase balance and favor the survival of Trypanosoma cruzi in macrophages.
Cruzipain (Cz), an antigen of Trypanosoma cruzi, mediates the activation of arginase involving p38 MAPK. In this work, it was studied whether the phosphorylation of MAPKs into macrophages (Mvarphi) could be induced by Cz and/or by the parasite. We found that Cz induced activation of p38, while the parasite produced phosphorylation of JNK and p44/p42. MAPK phosphorylation changed and JNK activation was blocked when Mvarphi were pre-incubated with Cz, before coming into contact with T. cruzi. We investigated the role of JNK inhibitor SP600125 on T. cruzi infection, since it also induces p38 phosphorylation. Thus, J774 cells were pre-treated with SP600125 and then infected with T. cruzi. This set of cells showed a decrease in nitric oxide (NO) production and an increase in arginase I expression. Another group of J774 cells was pre-treated with SP600125 and incubated with Cz before being infected with T. cruzi. This second group showed a greater reduction in NO production. These results can be correlated with the parasitic growth since the ex vivo treatment with SP600125 on adherent spleen cells (ASC) of BALB/c infected mice also increased the parasitic growth. Therefore, Cz and SP600125 favor the T. cruzi survival in Mvarphi by changing the iNOS/arginase balance.
Stempin
Cinthia C
CC
CIBICI-CONICET, Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende s/n, Ciudad Universitaria, 5000 Córdoba, Argentina.
Garrido
Vanina V
VV
Dulgerian
Laura R
LR
Cerbán
Fabio M
FM
D000818:Animals; D000873:Anthracenes / Q000494:pharmacology*; D001119:Arginase / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000494:pharmacology*; D007155:Immunologic Factors / Q000494:pharmacology*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000469:parasitology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D050296:Microbial Viability; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010766:Phosphorylation; D015800:Protozoan Proteins; D013154:Spleen / Q000276:immunology / Q000469:parasitology; D014349:Trypanosoma cruzi / Q000276:immunology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D000873:Anthracenes; D007155:Immunologic Factors; D015800:Protozoan Proteins; C432165:pyrazolanthrone; D009569:Nitric Oxide; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D003546:Cysteine Endopeptidases; C063214:cruzipain; D001119:Arginase