title: Human keratinocyte caspase-14 expression is altered in human epidermal 3D models by dexamethasone and by natural products used in cosmetics.
abstract: 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.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Keio University, 1-5-30, Shibakoen, Minatoku, Tokyo, 105-8512, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Kataoka
authors.forename: Kenji
authors.initials: K
authors.lastname: Hattori
authors.forename: Akira
authors.initials: A
authors.lastname: Date
authors.forename: Hiroomi
authors.initials: H
authors.lastname: Tamura
mesh_terms: D001688:Biological Products / Q000494:pharmacology; D053456:Caspase 14 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003358:Cosmetics / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D011965:Receptors, Glucocorticoid / Q000187:drug effects
chemical_list: D001688:Biological Products; D003358:Cosmetics; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone; D053456:Caspase 14