Trypanosoma cruzi infection induces nitric oxide production and S-nitrosylation of cellular FLIP in host cells

摘要

Previously, we demonstrated that Trypanosoma cruzi infection inhibited death receptor-mediated apoptosis in host cells, and that the parasite dramatically up-regulated cellular FLICE-like inhibitory protein (c-FLIP), a mammalian inhibitor specific for death receptor signaling. To elucidate the molecular mechanisms of c-FLIP up-regulation, we examined posttranscriptional regulation of c-FLIP expression in T. cruzi infected cells. In infected THP-1 cells, the nitrosylated protein was detected in the same size as c-FLIP (53 kDa). The expression profiles of the genes involved in nitric oxide (NO) biosynthesis, metabolism and signaling pathways showed that genes of glutathione peroxidase, inducible nitric oxide synthase (iNOS) and interleukin 8 were up-regulated in infected cells. These findings suggest that endogenously produced NO synthesized by NO synthase is a mediator of T. cruzi infection.