Replicative senescence enhances apoptosis induced by pemphigus autoimmune antibodies in human keratinocytes.
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.
Wang
Xin
X
The Myers Skin Biochemistry Laboratory, Department of Biological Chemistry, The Hebrew University, GivatRam, Jerusalem 91904, Israel.
Brégégère
François
F
Soroka
Yoram
Y
Frusic-Zlotkin
Marina
M
Milner
Yoram
Y
D017209:Apoptosis / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D061945:Caspase Inhibitors; D020169:Caspases / Q000096:biosynthesis; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D053938:DNA Fragmentation; D053222:Fas Ligand Protein; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D015603:Keratinocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000276:immunology; D010392:Pemphigus / Q000276:immunology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D001323:Autoantibodies; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D020169:Caspases