Caspase-14 expression by epidermal keratinocytes is regulated by retinoids in a differentiation-associated manner.
Caspase-14 is the only member of the caspase family that shows a restricted tissue expression. It is mainly confined to epidermal keratinocytes and in contrast to other caspases, is not activated during apoptosis induced by ultraviolet irradiation or cytotoxic substances. As it is cleaved under conditions leading to terminal differentiation of keratinocytes we suggested that caspase-14 plays a part in the physiologic cell death of keratinocytes leading to skin barrier formation. Here we show that retinoic acid, at concentrations inhibiting terminal differentiation of keratinocytes, strongly suppressed caspase-14 mRNA and protein expression by keratinocytes in monolayer culture and in a three-dimensional in vitro model of differentiating human epidermis (skin equivalent). By contrast, the expression of the caspases 3 and 8, which are both activated during conventional apoptosis, was increased and unchanged, respectively, after retinoic acid treatment. In addition to inhibition of differentiation in skin equivalents, retinoic acid treatment led to keratinocyte apoptosis and activation of caspase-3, both of which were undetectable in differentiated control skin equivalents. As this occurred in the absence of detectable caspase-14, our data demonstrate that caspase-14 is dispensable for keratinocyte apoptosis. The fact that in contrast to caspase-3 and caspase-8, caspase-14, similarly to other keratinocyte differentiation-associated proteins, is downregulated by retinoids, strongly suggests that this caspase, but not caspase-3 and -8, plays a part in terminal keratinocyte differentiation and skin barrier formation.
Rendl
Michael
M
Division of Immunology, Allergy, and Infectious Diseases, Department of Dermatology, University of Vienna Medical School, Austria.
Ban
Jozef
J
Mrass
Paul
P
Mayer
Christoph
C
Lengauer
Barbara
B
Eckhart
Leopold
L
Declerq
Wim
W
Tschachler
Erwin
E
D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D053456:Caspase 14; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D015536:Down-Regulation / Q000502:physiology; D000078404:Epidermal Cells; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000201:enzymology*; D007641:Keratolytic Agents / Q000494:pharmacology*; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000032:analysis; D014212:Tretinoin / Q000494:pharmacology*
D007641:Keratolytic Agents; D012333:RNA, Messenger; D014212:Tretinoin; C506446:CASP14 protein, human; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053456:Caspase 14; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases