Human keratinocyte caspase-14 expression is altered in human epidermal 3D models by dexamethasone and by natural products used in cosmetics

• Published in: Archives of Dermatological Research Vol. 305; no. 8; pp. 683 - 689
• Main Authors: Kataoka, Saori, Hattori, Kenji, Date, Akira, Tamura, Hiroomi
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.10.2013; Springer Nature B.V
• Subjects: Biological Products - pharmacology; Caspase 14 - biosynthesis; Caspase 14 - genetics; Caspase 14 - metabolism; Cell Line; Cosmetics - pharmacology; Dermatology; Dexamethasone - pharmacology; Epidermis - drug effects; Epidermis - metabolism; Humans; Keratinocytes - drug effects; Keratinocytes - metabolism; Medicine; Medicine & Public Health; Original Paper; Receptors, Glucocorticoid - drug effects; RNA, Messenger - biosynthesis; Caspase-14; Keratinocyte; Skin; Dexamethasone; Glucocorticoid
• ISSN: 0340-3696; 1432-069X
• DOI: 10.1007/s00403-013-1359-0

Caspase-14 is a cysteinyl-aspartate-specific proteinase that is specifically expressed in epidermal keratinocytes. Dysregulation of caspase-14 expression is implicated in impaired skin barrier formation. To elucidate the regulation of caspase-14 in differentiated keratinocytes, we characterized the expression of caspase-14 in normal human epidermal keratinocytes (NHEKs) and two types of three-dimensional (3D) human epidermis culture models, EPI-200 and EPI-201, via RT-PCR and immunoblot analyses. Caspase-14 expression was absent in subconfluent NHEKs, but was present in confluent NHEKs as well as those induced to differentiate by calcium. Caspase-14 expression levels in the 3D epidermis models were almost equal to that in the Ca 2+ -treated differentiated NHEKs. Despite the presence of caspase-14 expression in these models, caspase-14 activity was found only in the mature 3D skin model, EPI-200. This was confirmed by detection of a 17 kDa cleaved fragment of caspase-14 present only in the EPI-200 model. Since glucocorticoid (GC) receptor is required for skin barrier competence, we investigated whether the GC dexamethasone (Dex) and various natural components of common skin moisturizers affect caspase-14 expression in keratinocytes. Dex decreased caspase-14 expression in undifferentiated, but not differentiated, NHEKs. Conversely, Dex increased caspase-14 expression in both 3D skin models, although it did not alter caspase protease activity. Similar to treatment with Dex, treatment of the premature 3D skin mode, EPI-201 with a Galactomyces ferment filtrate markedly increased expression of caspase-14. Further, these results suggest that the effect of Dex, or lack thereof, on caspase-14 expression is dependent on the stage of keratinocyte differentiation.