“JNK inhibitor SP600125 induces p38 activation and increases Trypanosoma cruzi growth in macrophages by shifting the balance of iNOS and arginase activities. Similar effects are produced by cruzipain”

STEMPIN, C; GARRIDO, V; DULGERIAN, L; CERBAN, F

Rio de Janeiro, Brazil

Congreso; 13th International Congress of Immunology; 2007

Brazilian Society of Immunology

Cruzipain (Cz), an antigen of Trypanosoma cruzi, mediates the activation of arginase involving p38 MAPK. In this work, it is studied if the phosphorylation of MAPKs into macrophages (Mf) can be induced by Cz and/or by the parasite. We have found that Cz induces the activation of p38, while the parasite produces the phosphorylation of JNK and p44/p42. MAPK phosphorylation changes and JNK activation is blocked when the Mf is pre-incubated with Cz, before to be in contact with T. cruzi. We have 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 diminution in nitric oxide (NO) production and increment of arginase I expression. Other group of J774 cells was pre-treated with SP600125 and incubated with Cz before to be infected with T. cruzi. This second group showed greater diminution in NO production. These results can also be correlated with the parasite growth, since SP600125 favors parasite proliferation in infected Mf. The ex-vivo treatment with SP600125 on adherent spleen cells (ASC) of BALB/c infected mice also increases the number of intracellular parasites. This is the first time in which the impact of SP600125 in the parasite infection is demonstrated. Our results also point that JNK pathway can control T. cruzi growth into the Mf. In addition, Cz should be involved in the survival of T. cruzi into the Mf by changing MAPK phosphorylation.

Key words: arginase, nitric oxide, MAPK, Trypanosoma cruzi, macrophage