Arginase induction promotes Trypanosoma cruzi intracellular replication in Cruzipain-treated J774 cells through the activation of multiple signaling pathways

CINTHIA C. STEMPIN, TAMARA B. TANOS, OMAR A. COSO AND FABIO M. CERBAN

WILEY-VCH Verlag GmbH & Co. KGaA

Lugar: Weinheim, Germany; Año: 2004 vol. 34 p. 200 - 200

iven that arginase activation may effectively influence nitric oxide (NO) production in macrophages,we investigatedd the intracellular signals that regulate l-arginine metabolism and its influence on Trypanosoma cruzi growth. We demonstrate that cruzipain (Cz), a parasite antigen, induces arginase I expression in J774 cells, and the pretreatment of Cz-treated cells with N-omega-hydroxy-arginine (arginase inhibitor) leads to a dramatic decrease in amastigote growth. The study of intracellular signals shows that genistein [tyrosine kinase (TK) inhibitor], KT5720 [protein kinase (PK) A inhibitor] and SB203580 [p38 mitogen-activated protein kinase (MAPK) inhibitor] significantly decrease Cz-induced arginase activation.However, calphostin C (PKC inhibitor) and PD98059 [p44/p42 MAPK kinase (MEK)inhibitor] did not cause a significant change. To determine if signaling pathways triggered by Cz were involved in the T. cruzi growth, we studied the effect of those inhibitors. In Cz-treated cel