title: In vivo blockade of pemphigus vulgaris acantholysis by inhibition of intracellular signal transduction cascades.
abstract: BACKGROUND
  Pemphigus vulgaris (PV) is an autoimmune disease characterized by mucocutaneous intraepithelial blisters and pathogenic autoantibodies against desmoglein 3. The mechanism of blister formation in pemphigus has not been defined; however, in vitro data suggest a role for activation of intracellular signalling cascades.
  
  
  OBJECTIVE
  To investigate the contribution of these signalling pathways to the mechanism of PV IgG-induced acantholysis in vivo.
  
  
  METHODS
  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.
  
  
  RESULTS
  Inhibitors of tyrosine kinases, phospholipase C, calmodulin and the serine/threonine kinase protein kinase C prevented PV IgG-induced acantholysis in vivo.
  
  
  CONCLUSIONS
  These observations strongly support the role of intracellular signalling cascades in the molecular mechanism of PV IgG-induced acantholysis.
authors.affiliation: Department of Dermatology, University Clinic of Navarra, School of Medicine, University of Navarra, PO Box 4209, Pamplona, Navarra, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Sánchez-Carpintero
authors.forename: A
authors.initials: A
authors.lastname: España
authors.forename: B
authors.initials: B
authors.lastname: Pelacho
authors.forename: N
authors.initials: N
authors.lastname: López Moratalla
authors.forename: D S
authors.initials: DS
authors.lastname: Rubenstein
authors.forename: L A
authors.initials: LA
authors.lastname: Diaz
authors.forename: M J
authors.initials: MJ
authors.lastname: López-Zabalza
mesh_terms: D000051:Acantholysis / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D000818:Animals; D015820:Cadherins / Q000276:immunology; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000502:physiology; D051184:Desmoglein 3; D004195:Disease Models, Animal; D006801:Humans; D007116:Immunization, Passive; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010392:Pemphigus / Q000150:complications*; D011494:Protein Kinases / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000502:physiology
chemical_list: D015820:Cadherins; D002147:Calmodulin; C071894:DSG3 protein, human; D051184:Desmoglein 3; D007074:Immunoglobulin G; D011494:Protein Kinases; D010738:Type C Phospholipases