Document Detail


Apoptosis is not required for acantholysis in pemphigus vulgaris.
MedLine Citation:
PMID:  18987254     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The autoimmune blistering skin disease pemphigus vulgaris (PV) is caused primarily by autoantibodies against desmosomal cadherins. It was reported that apoptosis can be detected in pemphigus skin lesions and that apoptosis can be induced by PV-IgG in cultured keratinocytes. However, the role of apoptosis in PV pathogenesis is unclear at present. In this study, we provide evidence that apoptosis is not required for acantholysis in PV. In skin lesions from two PV patients, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) positivity, but not cleaved caspase-3, was detected in single keratinocytes in some lesions but was completely absent in other lesions from the same patients. In cultures of human keratinocytes (HaCaT and normal human epidermal keratinocytes), PV-IgG from three different PV patients caused acantholysis, fragmented staining of Dsg 3 staining, and cytokeratin retraction in the absence of nuclear fragmentation, TUNEL positivity, and caspase-3 cleavage and hence in the absence of detectable apoptosis. To further rule out the contribution of apoptotic mechanisms, we used two different approaches that are effective to block apoptosis induced by various stimuli. Inhibition of caspases by z-VAD-fmk as well as overexpression of Fas-associated death domain-like interleukin-1beta-converting enzyme (FLICE)-like inhibitory proteins FLIP(L) and FLIP(S) to inhibit receptor-mediated apoptosis did not block PV-IgG-induced effects, indicating that apoptosis was not required. Taken together, we conclude that apoptosis is not a prerequisite for skin blistering in PV but may occur secondary to acantholysis.
Authors:
Enno Schmidt; Judith Gutberlet; Daniela Siegmund; Daniela Berg; Harald Wajant; Jens Waschke
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-11-05
Journal Detail:
Title:  American journal of physiology. Cell physiology     Volume:  296     ISSN:  0363-6143     ISO Abbreviation:  Am. J. Physiol., Cell Physiol.     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2009-01-05     Completed Date:  2009-02-26     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901225     Medline TA:  Am J Physiol Cell Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  C162-72     Citation Subset:  IM    
Affiliation:
Department of Dermatology, University of Würzburg, Würzburg, Germany.
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MeSH Terms
Descriptor/Qualifier:
Acantholysis / immunology,  metabolism,  pathology*
Amino Acid Chloromethyl Ketones / pharmacology
Anoikis
Apoptosis* / drug effects
Biopsy
CASP8 and FADD-Like Apoptosis Regulating Protein / genetics,  metabolism
Caspase 3 / metabolism
Cell Line
Cell Nucleus Shape
Cysteine Proteinase Inhibitors / pharmacology
DNA Fragmentation
Desmoglein 3 / metabolism
Humans
Immunoglobulin G / blood*
Immunohistochemistry
In Situ Nick-End Labeling
Keratinocytes / drug effects,  immunology,  metabolism,  pathology*
Keratins / metabolism
Pemphigus / immunology,  metabolism,  pathology*
Transfection
Chemical
Reg. No./Substance:
0/Amino Acid Chloromethyl Ketones; 0/CASP8 and FADD-Like Apoptosis Regulating Protein; 0/Cysteine Proteinase Inhibitors; 0/DSG3 protein, human; 0/Desmoglein 3; 0/Immunoglobulin G; 0/benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; 68238-35-7/Keratins; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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