Replicative senescence enhances apoptosis induced by pemphigus autoimmune antibodies in human keratinocytes

FEBS Lett. 2004 Jun 4;567(2-3):281-6. doi: 10.1016/j.febslet.2004.04.083.

Abstract

We have recently shown that skin lesions of the autoimmune disease pemphigus vulgaris are associated with Fas-mediated apoptosis. Here, we describe the induction of the Fas-dependent apoptosis pathway in cultured keratinocytes by pemphigus vulgaris autoantibodies (PV-IgG), as seen from a variety of cellular, morphological and biochemical parameters. All apoptotic characters appear stronger and faster in aged cultures than in young, showing increased susceptibility of senescent keratinocytes to PV-IgG-mediated apoptotic death and culture lesions. Together with immunosenescence, this phenomenon may explain the late onset of pemphigus disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / immunology*
  • Autoantibodies / immunology*
  • Caspase Inhibitors
  • Caspases / biosynthesis
  • Cells, Cultured
  • Cellular Senescence / physiology*
  • Cysteine Proteinase Inhibitors / pharmacology
  • DNA Fragmentation
  • Fas Ligand Protein
  • Humans
  • Immunoglobulin G / immunology
  • Keratinocytes / cytology*
  • Keratinocytes / immunology*
  • Keratinocytes / metabolism
  • Membrane Glycoproteins / biosynthesis
  • Membrane Glycoproteins / immunology
  • Pemphigus / immunology*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Autoantibodies
  • Caspase Inhibitors
  • Cysteine Proteinase Inhibitors
  • FASLG protein, human
  • Fas Ligand Protein
  • Immunoglobulin G
  • Membrane Glycoproteins
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53
  • Caspases