Pathogenic monoclonal antibody against desmoglein 3 augments desmoglein 3 and p38 MAPK phosphorylation in human squamous carcinoma cell line.
Pemphigus vulgaris is an autoimmune blistering disease characterized by cell-cell detachment of epidermal cells. Autoantibody against desmoglein (Dsg) 3, a transmembrane glycoprotein that mediates the association of desmosomes, plays a major role in blistering in pemphigus vulgaris (PV). The mechanisms of autoantibody-induced acantholysis have not been clarified. We previously reported that PV-IgG induces phosphorylation of Dsg3, decreases Dsg3 on the cell surface and forms Dsg3-depleted desmosomes in cultured keratinocytes, and that cell treatment with a potent pathogenic monoclonal antibody against Dsg3 (AK23 mAb) decreases the amount of Dsg3 in cultured keratinocytes. Although the precise mechanisms remain unclear, we have proposed the involvement of intracellular signal transduction resulting from the binding of autoantibodies to Dsg3. In this study, we examined whether AK23 mAb augments phosphorylation of Dsg3 and p38 mitogen-activating protein kinase (MAPK) in a human squamous cell line, DJM-1 cells. AK23 mAb increased serine phosphorylation of Dsg3 and augmented activation levels of p38 MAPK. These results indicate that antibodies bind to Dsg3, but not other antigens, in the IgG fraction and can induce activation of signal transduction.
Kawasaki
Yuki
Y
Department of Dermatology, Gifu University School of Medicine, Gifu, 501-1194, Japan.
Aoyama
Yumi
Y
Tsunoda
Kazuyuki
K
Amagai
Masayuki
M
Kitajima
Yasuo
Y
D000276:Adjuvants, Immunologic / Q000502:physiology* / Q000633:toxicity; D000911:Antibodies, Monoclonal / Q000502:physiology* / Q000633:toxicity; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D045744:Cell Line, Tumor; D051184:Desmoglein 3 / Q000276:immunology* / Q000378:metabolism*; D004789:Enzyme Activation / Q000276:immunology; D006801:Humans; D010766:Phosphorylation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; C071894:DSG3 protein, human; D051184:Desmoglein 3; D048051:p38 Mitogen-Activated Protein Kinases