Involvement of the Apoptotic Mechanism in Pemphigus Foliaceus Autoimmune Injury of the Skin
Year: 2009
Type: article
Abstract: Pemphigus foliaceus (PF) is an organ-specific autoimmune skin disease characterized by subcorneal epidermal cell detachment (acantholysis) and pathogenic autoantibodies against desmoglein 1. The mechanism responsible for pemphigus autoantibody-induced epidermal injury is not fully understood. In this study, we used the IgG passive transfer mouse model of PF to investigate the relevance of the apoptotic mechanism in pemphigus pathogenesis. TUNEL-positive epidermal cells and increased oligonucleosomes in the epidermal cytosolic fractions were detected in the diseased mice. Time course study reveals that TUNEL-positive epidermal cells appear before intraepidermal blisters. Moreover, the proapoptotic factor Bax was up-regulated at the earlier time points (2 and 4 h), whereas the antiapoptotic factor Bcl-x(L) was down-regulated at the later time points (6, 8, and 20 h) post-PF IgG injection by Western blot analysis. The active forms of caspase-3 and -6 were detected at the later time period (6, 8, and 20 h). Administration of Ac-DEVD-cmk, a peptide-based caspase-3/7 inhibitor, protected mice from developing intraepidermal blisters and clinical disease induced by PF IgG. The same protective effect was also observed using a broad-spectrum caspase inhibitor, Bok-D-fmk. Collectively, these findings show that biochemical events of apoptosis are provoked in the epidermis of mice injected with PF autoantibodies. Caspase activation may contribute to acantholytic blister formation in PF.
Source: The Journal of Immunology
Authors: Ning Li, Minglang Zhao, Jinzhao Wang, Zhi Liu, Luis A Diaz
Institution: University of North Carolina at Chapel Hill
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1185513462, Role of Apoptosis in Pemphigus, Immunopathogenesis of Bullous Pemphigoid, G2701919183, G2778470008, Pemphigus and Pemphigoid, G3055137528, G3909552190, The Mechanism of IVIG Action in Pemphigus, G5109019395, G5267828232, IMMUNOPATHOGENESIS OF BULLOUS PEMPHIGOID, Role of Glycosylation of Dsg1 in Pemphigus acantholysis, Etiology and Pathogenesis of Pemphigus, G9000033810
OpenAlex ID: W1545566206