Tumor necrosis factor alpha induced by Trypanosoma cruzi infection mediates inflammation and cell death in the liver of infected mice.
Trypanosoma cruzi (T. cruzi) infected C57BL/6 mice developed a progressive fatal disease due to an imbalance in the profile of circulating related compounds accompanying infection like tumor necrosis factor alpha (TNFalpha). TNFalpha has been proposed as an important effector molecule in apoptosis. In this work, we evaluate inflammation and the proteins involved in apoptotic process in liver of infected mice and the role of TNFalpha. C57BL6/mice were infected subcutaneously with 100 viable trypomastigotes of Tulahuén strain of T cruzi. One set of these animals were treated with 375 microg of antihuman TNFalpha blocking antibody. Animals were sacrificed at 14 days post-infection (p.i).The analyses of Bcl-2 family proteins revealed an increase of the pro-apoptotic proteins Bax and tBid in T. cruzi-infected mice. Compared with control animals, cytochrome c release was increased. Apoptosis was also induced in infected mice. Anti-TNFalpha treatment decreases hepatic apoptosis. Our results suggest that T. cruzi infection induces programmed cell death in the host liver by increase of TNFalpha production, associated with TNF-R1 over-expression, that set in motion the Bid cleavage and mitochondrial translocation, Bax mitochondrial translocation, cytochrome c release, and ultimately apoptosis induction.
Ronco
Maria T
MT
Instituto de Fisiología Experimental - CONICET, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Argentina.
Francés
Daniel E
DE
Ingaramo
Paola I
PI
Quiroga
Ariel D
AD
Alvarez
Maria L
ML
Pisani
Gerardo B
GB
Revelli
Silvia S
SS
Carnovale
Cristina E
CE
D000818:Animals; D051023:BH3 Interacting Domain Death Agonist Protein / Q000276:immunology; D016923:Cell Death / Q000276:immunology*; D014355:Chagas Disease / Q000276:immunology*; D045304:Cytochromes c / Q000378:metabolism; D006801:Humans; D020287:In Situ Nick-End Labeling; D007249:Inflammation / Q000276:immunology / Q000382:microbiology; D008099:Liver / Q000166:cytology / Q000276:immunology* / Q000469:parasitology*; D051379:Mice; D008810:Mice, Inbred C57BL; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000276:immunology; D014349:Trypanosoma cruzi / Q000276:immunology* / Q000472:pathogenicity; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology*; D051028:bcl-2-Associated X Protein / Q000276:immunology; D051020:bcl-X Protein / Q000276:immunology
D051023:BH3 Interacting Domain Death Agonist Protein; C494812:Bcl2l1 protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D045304:Cytochromes c