2011
DOI: 10.4061/2011/563091
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The Caspase Pathway as a Possible Therapeutic Target in Experimental Pemphigus

Abstract: Apoptosis plays a role in pemphigus IgG-dependent acantholysis; theoretically, the blockade of the caspase pathway could prevent the blistering that is caused by pemphigus autoantibodies. Using this strategy, we attempted to block the pathogenic effect of pemphigus IgG in Balb/c mice by using the caspase inhibitor Ac-DEVD-CMK. This inhibitor was administrated before the injection of pemphigus IgG into neonatal mice. The main results of the present investigation are as follows: (1) pemphigus IgG induces intraep… Show more

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Cited by 10 publications
(25 citation statements)
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“…In our PV models, no evidence for a robust caspase-3 activation has been revealed, as it would be expected in case of apoptosis [ 15 ]. However, caspase inhibitors were reported to reduce blistering in neonatal mice injected with PVIgG [ 29 , 30 ]. Furthermore, low-level caspase-3 activity has been associated with keratinocyte terminal differentiation [ 19 , 56 ] but was not detected by immunoblotting applied here ( Fig.…”
Section: Resultsmentioning
confidence: 99%
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“…In our PV models, no evidence for a robust caspase-3 activation has been revealed, as it would be expected in case of apoptosis [ 15 ]. However, caspase inhibitors were reported to reduce blistering in neonatal mice injected with PVIgG [ 29 , 30 ]. Furthermore, low-level caspase-3 activity has been associated with keratinocyte terminal differentiation [ 19 , 56 ] but was not detected by immunoblotting applied here ( Fig.…”
Section: Resultsmentioning
confidence: 99%
“…Based on the initial observation of TUNEL (TdT-mediated dUTP-biotin nick end labeling)-positive cells in lesional skin of PV patients [ 27 , 28 ], apoptosis was also proposed to be involved in PV pathogenesis. Independent reports on caspase activation in the neonatal PV mouse model and reduced blistering after caspase-3 inhibitor treatment supported this claim [ 29 , 30 ]. Accordingly, “acantholysis and apoptosis” were discussed to be “inseparable in PV”, invoking a process termed “apoptolysis” where acantholysis proceeds along apoptotic pathways resulting in cell death [ 31 , 32 ].…”
Section: Introductionmentioning
confidence: 93%
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“…Agregar pimecrolimus 1% tópico al tratamiento con prednisona y azatioprina pareciera ser efectivo 20 . Tacrolimus sistémico 21 , antimaláricos nuevos como la daphentina 22 , administración de altas dosis de péptidos de Dsg3 11 , inhibidores de caspasas 23 y el transplante alogénico de médula ósea 24 podrían considerarse como alternativas a futuro.…”
Section: Discussionunclassified
“…[42] Because apoptosis sensitizes the cells to the acantholytic effects of PV-IgG, the blockade of the caspase pathway could prevent the blistering in pemphigus. Pacheco-Tovar et al [43] studied the effects of caspase inhibitor Ac-DEVD-CMK in BALB/c mice where pemphigus had been induced experimentally and found the caspase inhibitor to block apoptosis and prevent blistering. It has also been studied that hyperadhesion of desmosomes makes them more resistant to acantholysis in experimental PV.…”
Section: Diagnosis Of Autoimmune Bullous Diseases: From Immunoflouresmentioning
confidence: 98%