Universität zu Köln

Kuechler, Sarah, Henkes, Dominika, Eckl, Katja-Martina, Ackermann, Katharina, Plendl, Johanna, Korting, Hans-Christian, Hennies, Hans-Christian and Schaefer-Korting, Monika (2011). Hallmarks of Atopic Skin Mimicked In Vitro by Means of a Skin Disease Model Based on FLG Knock-down. ATLA-Altern. Lab. Anim., 39 (5). S. 471 - 481. NOTTINGHAM: FRAME. ISSN 0261-1929

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Abstract

Loss-of-function mutations in the filaggrin gene (FLG) are a strong predisposing factor for atopic dermatitis, although their relevance to the disease pathomechanism needs further elucidation. The generation of an in vitro model of atopic skin would not only permit further evaluation of the underlying pathogenetic mechanisms and the testing of new treatment options, but would also allow toxicological studies to be performed in a simple, rapid and inexpensive manner. In this study, we have knocked down FLG expression in human keratinocytes and created three-dimensional skin models, which we used to investigate the impact of FLG on epidermal maturation and on skin absorption and its response to irritation. Histopathological evaluation of the skin models showed impaired epidermal differentiation in the FLG knock-down model. In addition, skin irritation induced by an application of sodium dodecyl sulphate resulted in significantly higher lactate dehydrogenase leakage, and interleukin (IL)-6 and IL-8 levels, than in the control model. To assess the effect of filaggrin deficiency on skin absorption of topically applied agents, we quantified the percutaneous absorption of lipophilic and hydrophilic model drugs, finding clinical relevance only for lipophilic drugs. This study clearly demonstrates that important clinical characteristics of atopic skin can be mimicked by using in vitro skin models. The FLG knock-down construct is the first step toward an in vitro model that allows clinical and toxicological studies of atopic-like skin.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kuechler, Sarah UNSPECIFIED UNSPECIFIED UNSPECIFIED Henkes, Dominika UNSPECIFIED UNSPECIFIED UNSPECIFIED Eckl, Katja-Martina UNSPECIFIED UNSPECIFIED UNSPECIFIED Ackermann, Katharina UNSPECIFIED UNSPECIFIED UNSPECIFIED Plendl, Johanna UNSPECIFIED UNSPECIFIED UNSPECIFIED Korting, Hans-Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Hennies, Hans-Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Schaefer-Korting, Monika UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-488278
DOI:	10.1177/026119291103900508
Journal or Publication Title:	ATLA-Altern. Lab. Anim.
Volume:	39
Number:	5
Page Range:	S. 471 - 481
Date:	2011
Publisher:	FRAME
Place of Publication:	NOTTINGHAM
ISSN:	0261-1929
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language RECONSTRUCTED HUMAN EPIDERMIS; PERCUTANEOUS-ABSORPTION; BARRIER ABNORMALITY; ANIMAL-MODELS; DERMATITIS; FILAGGRIN; IRRITATION; FIBROBLASTS; ICHTHYOSIS; MECHANISMS Multiple languages Medicine, Research & Experimental Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/48827