title: Regulation of caspase 14 expression in keratinocytes by inflammatory cytokines--a possible link between reduced skin barrier function and inflammation?
abstract: Caspase 14 is a unique member of the cysteinyl aspartate-specific proteinase family. Its expression is confined primarily to cornified epithelium such as the skin. Caspase 14 has been associated with the processing of filaggrin monomers and the development of natural moisturising factors of the skin, and thus, it could be speculated that caspase 14 dysregulation is implicated in the development of an impaired skin barrier function. We have investigated the regulation of caspase 14 transcription in cultured primary keratinocytes following stimulation with a number of factors present in inflamed skin, including T(H)1- and T(H)2-associated cytokines in addition to LPS and peptidoglycan. In particular, we found that T(H)2-associated cytokines reduced the caspase 14 mRNA level significantly. Furthermore, we found that the expression of caspase 14 was reduced in skin biopsies from patients with atopic dermatitis (AD), psoriasis and contact dermatitis, further supporting a role for this kinase in inflammatory skin conditions. Hence, the regulation of caspase 14 levels provides a possible link between impaired skin barrier function and inflammatory reactions in skin diseases such as AD and may offer an explanation to the skin barrier dysfunction in inflamed skin lesions.
authors.affiliation: Department of Dermato-venereology, Aarhus University Hospital, Aarhus C, Denmark.
authors.forename: Malene
authors.initials: M
authors.lastname: Hvid
authors.forename: Claus
authors.initials: C
authors.lastname: Johansen
authors.forename: Bent
authors.initials: B
authors.lastname: Deleuran
authors.forename: Kaare
authors.initials: K
authors.lastname: Kemp
authors.forename: Mette
authors.initials: M
authors.lastname: Deleuran
authors.forename: Christian
authors.initials: C
authors.lastname: Vestergaard
mesh_terms: D001706:Biopsy; D016022:Case-Control Studies; D053456:Caspase 14 / Q000187:drug effects / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000502:physiology*; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D003876:Dermatitis, Atopic / Q000378:metabolism* / Q000473:pathology; D003877:Dermatitis, Contact / Q000378:metabolism* / Q000473:pathology; D000091344:Filaggrin Proteins; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D018793:Interleukin-13 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D007381:Intermediate Filament Proteins / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D011565:Psoriasis / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D012867:Skin / Q000473:pathology / Q000503:physiopathology*
chemical_list: D016207:Cytokines; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D018793:Interleukin-13; D007381:Intermediate Filament Proteins; D012333:RNA, Messenger; D015847:Interleukin-4; D007371:Interferon-gamma; D053456:Caspase 14