Tumor necrosis factor related apoptosis inducing ligand triggers apoptosis in dividing but not in differentiating human epidermal keratinocytes.
Using serial analysis of gene expression we have previously identified the expression of several pro-apoptotic and anti-apoptotic genes in cultured human primary epidermal keratinocytes, including tumor necrosis factor related apoptosis inducing ligand (TRAIL). TRAIL is a potent inducer of apoptosis in transformed and tumor cell lines, but usually not in other cells. Here we present a study on the effect of TRAIL on cultured keratinocytes. It is shown that differentiated and undifferentiated keratinocytes undergo apoptosis after addition of TRAIL to the medium as determined by morphologic and biochemical criteria, such as cellular shrinkage and activation of caspases. The sensitivity for TRAIL differs greatly between undifferentiated and differentiating keratinocytes, however, with undifferentiated cells being much more susceptible to apoptosis. Commitment to terminal differentiation in the absence of TRAIL does not in itself induce apoptosis. In contrast to the promyelocytic cell line HL60, internucleosomal DNA fragmentation is not observed in keratinocytes, as assessed by flow cytometric analysis and agarose gel electrophoresis. Interestingly, the prime effector of DNA fragmentation, DNA fragmentation factor of 40 kDa (DFF40), is expressed in keratinocytes, yet internucleosomal cleavage fails to occur. Our data indicate that programmed cell death during keratinocyte differentiation is distinct from receptor-mediated apoptosis in response to a death ligand.
Jansen
Bastiaan J H
BJ
Department of Dermatology, University Medical Center Nijmegen, Nijmegen, The Netherlands. b.jansen@ncmls.kun.nl
van Ruissen
Fred
F
Cerneus
Stefanie
S
Cloin
Wendy
W
Bergers
Mieke
M
van Erp
Piet E J
PE
Schalkwijk
Joost
J
D000970:Antineoplastic Agents / Q000494:pharmacology*; D051017:Apoptosis Regulatory Proteins; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D053938:DNA Fragmentation / Q000187:drug effects / Q000502:physiology*; D003851:Deoxyribonucleases / Q000235:genetics; D000078404:Epidermal Cells; D015870:Gene Expression; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000502:physiology*; D008024:Ligands; D008562:Membrane Glycoproteins / Q000235:genetics; D000075223:Poly-ADP-Ribose Binding Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000494:pharmacology*
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D008024:Ligands; D008562:Membrane Glycoproteins; D000075223:Poly-ADP-Ribose Binding Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; C113696:DFFB protein, human; D003851:Deoxyribonucleases; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases