Methyl‐β‐cyclodextrin concurs with interleukin (<scp>IL</scp>)‐4, <scp>IL</scp>‐13 and <scp>IL</scp>‐25 to induce alterations reminiscent of atopic dermatitis in reconstructed human epidermis

Vuyst, Évelyne De; Giltaire, Séverine; Rouvroit, Catherine Lambert de; Malaisse, Jérémy; Mound, Abdallah; Bourtembourg, Maureen; Poumay, Yves; Nikkels, Arjen F.; Chrétien, Aline; Salmon, Michel

doi:10.1111/exd.13113

Cited by 32 publications

(33 citation statements)

References 9 publications

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“…RHE tissues were produced as described and grown according to the manufacturer's instructions (StratiCELL, Isnes, Belgium). To reproduce the morphological and functional aspects of AD, RHE were exposed to Th2 cytokines IL‐4, IL‐13, IL‐25, as previously described . Keratinocytes from AD biopsies were also used to reconstruct human epidermis without Th2 cytokine treatment.…”

Section: Experimental Designmentioning

confidence: 99%

On the relevance of an in vitro reconstructed human epidermis model for drug screening in atopic dermatitis

Hubaux

Bastin

Salmon

2018

Experimental Dermatology

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Recent advances in the development of human‐based in vitro models offer new tools for drug screening and mechanistic investigations of new therapeutic agents. However, there is a lack of evidence that disease models respond favourably to potential drug candidates. Atopic dermatitis (AD) is a very common disease associated with an altered skin barrier and chronic inflammation. Here, we demonstrate that the AD‐like features of a reconstructed human epidermis (RHE) model treated with Th2 cytokines are reversed in the presence of molecules known to have a beneficial effect on damaged skin as a result of modulating various signalling cascades including the Liver X Receptors and JAK/STAT pathways. This work shows that standardized and reproducible RHE are relevant models for therapeutic research assessing new drug candidates aiming to restore epidermal integrity in an inflammatory environment.

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Section: Experimental Designmentioning

confidence: 99%

On the relevance of an in vitro reconstructed human epidermis model for drug screening in atopic dermatitis

Hubaux

Bastin

Salmon

2018

Experimental Dermatology

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“…Concordantly, stimulation with a combination of TNF‐α, IL‐4, IL‐13 and the Toll‐like receptor 3 ligand Poly I:C resulted in differential expression of 26 genes including key markers of atopic skin. A further study included methyl‐β‐cyclodextrin, a molecule that extracts cholesterol from plasma membranes and thus disrupts lipid microdomains . The combination of membrane cholesterol depletion and the Th2 cytokines IL‐4/IL‐13 and IL‐25 also elicited an AD‐like phenotype.…”

Section: Alternative Methods In Research On Atopic Dermatitismentioning

confidence: 99%

“…A further study included methylβ-cyclodextrin, a molecule that extracts cholesterol from plasma membranes and thus disrupts lipid microdomains. [55] The combination of membrane cholesterol depletion and the Th2 cytokines IL-4/IL-13 and IL-25 also elicited an AD-like phenotype. In fact, these data demonstrate the impact of pathophysiologically relevant mediators can be easily studied in vitro.…”

Section: Epidermal Models Emulating Characteristics Of Admentioning

confidence: 99%

Alternatives to animal testing in basic and preclinical research of atopic dermatitis

Löwa

Jevtić

Gorreja

et al. 2018

Experimental Dermatology

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Atopic dermatitis (AD) is a chronic inflammatory skin disease of increasing prevalence, especially in industrialized countries. Roughly 25% of the children and 1%-3% of adults are affected. Although significant progress has been made in the understanding of the pathogenesis of AD, many aspects remain poorly understood. Moreover, there is a pressing need for improved therapeutic options. Studies to elucidate the pathophysiological pathways of AD and to identify novel therapeutic targets over the last few decades have been conducted almost exclusively in animal models. However, in vitro approaches such as 3D skin disease models have recently emerged due to an increasing awareness of distinct interspecies-related differences that hamper the effective translation of results from animal models to humans. In addition, there is growing political and social pressure to develop alternatives to animal models according to the 3Rs principle (reduction, refinement and replacement of animal models). K E Y W O R D S3R approach, atopic dermatitis, preclinical dermatology, skin equivalents, skin model

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“…Based on the “inside‐out signalling” established in AD, epidermis is exposed to type 2 immune cytokines such as IL‐4 and IL‐13 and produces the type 2 immune cytokine, IL‐25. De Vuyst et al used reconstructed human epidermis (RHE) and exposed RHE to a mixture of these three cytokines to mimic the clinical setting in AD. RHE was in addition treated with methyl‐β‐cyclodextrin (MβCD).…”

Section: New Models For Ad: Investigating the Pathogenesis And Monitomentioning

confidence: 99%

“…Most importantly, TSLP, that is the epithelial cytokine effective upstream and inducing the Th2 pathway, remained highly upregulated in RHE exposed to type 2 cytokines and MβCD2. Thus, this model may be used as a screening tool to identify compounds that prevent or treat the epidermal consequences of the dysregulated cytokine milieu that is associated with AD …”

Section: New Models For Ad: Investigating the Pathogenesis And Monitomentioning

confidence: 99%

A new era for translational atopic dermatitis research and management

Kabashima

Biedermann

2018

Experimental Dermatology

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Methyl‐β‐cyclodextrin concurs with interleukin (IL)‐4, IL‐13 and IL‐25 to induce alterations reminiscent of atopic dermatitis in reconstructed human epidermis

Cited by 32 publications

References 9 publications

On the relevance of an in vitro reconstructed human epidermis model for drug screening in atopic dermatitis

On the relevance of an in vitro reconstructed human epidermis model for drug screening in atopic dermatitis

Alternatives to animal testing in basic and preclinical research of atopic dermatitis

A new era for translational atopic dermatitis research and management

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