In vivo blockade of pemphigus vulgaris acantholysis by inhibition of intracellular signal transduction cascades
Sánchez-Carpintero I, España A, Pelacho B, López Moratalla N, Rubenstein DS, Diaz LA, López-Zabalza MJ.
Pemphigus vulgaris (PV) is an autoimmune disease characterized by mucocutaneous intraepithelial blisters and pathogenic autoantibodies against desmoglein. The mechanism of blister formation in pemphigus has not been defined; however, in vitro data suggest a role for activation of intracellular signalling cascades.
To investigate the contribution of these signalling pathways to the mechanism of PV IgG-induced acantholysis in vivo.
We used the passive transfer mouse model. Mice were injected with IgG fractions of sera from a patient with PV, with or without pretreatment with inhibitors of proteins that mediate intracellular signalling cascades.
Inhibitors of tyrosine kinases, phospholipase C, calmodulin and the serine/threonine kinase protein kinase C prevented PV IgG-induced acantholysis in vivo.
These observations strongly support the role of intracellular signalling cascades in the molecular mechanism of PV IgG-induced acantholysis.
CITATION Br J Dermatol. 2004 Sep;151(3):565-70