ADAM10-mediated E-cadherin release is regulated by proinflammatory cytokines and modulates keratinocyte cohesion in eczematous dermatitis

Thorsten Maretzky; Felix Scholz; Bente Köten; Ehrhardt Proksch; Paul Saftig; Karina Reiss

doi:10.1038/sj.jid.5701242

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ADAM10-mediated E-cadherin release is regulated by proinflammatory cytokines and modulates keratinocyte cohesion in eczematous dermatitis

Journal article

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Peer reviewed

ADAM10-mediated E-cadherin release is regulated by proinflammatory cytokines and modulates keratinocyte cohesion in eczematous dermatitis

Thorsten Maretzky, Felix Scholz, Bente Köten, Ehrhardt Proksch, Paul Saftig and Karina Reiss

Journal of investigative dermatology, Vol.128(7), pp.1737-1746

07/2008

DOI: 10.1038/sj.jid.5701242

PMID: 18200054

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Abstract

Acute eczema is an inflammatory skin disease characterized by the formation of small intraepidermal blisters, reduction of the adhesion molecule E-cadherin from the keratinocyte surface, and impaired keratinocyte cohesion. Here, we reveal that the disintegrin and metalloprotease ADAM10 is critically involved in regulating E-cadherin cell-surface expression in cultured primary human keratinocytes and in diseased human skin. Proinflammatory cytokines, transforming growth factor-beta, and lipopolysaccharide led to increased release of soluble E-cadherin by activating mitogen-activated protein kinase signaling in cultured keratinocytes. Moreover, these stimuli decreased the amount of pro-ADAM10 and increased the level of the active protease, leading to loss of E-cadherin from the cell surface and decreased keratinocyte cohesion. In situ examination and immunoblot analyses of E-cadherin and ADAM10 expression in lesional skin of eczema revealed that the reduction of E-cadherin expression in areas of blister formation closely correlated with increased level of ADAM10 expression and elevated E-cadherin shedding. Our data suggest that ADAM10-mediated E-cadherin proteolysis leads to the impaired cohesion of keratinocytes observed in eczematous dermatitis and provide previously unreported insights into the understanding of the molecular mechanisms involved in inflammatory diseases with loss in epithelial integrity.

Interleukin-1beta - pharmacology

ADAM Proteins - physiology

Amyloid Precursor Protein Secretases - physiology

Cadherins - metabolism

Humans

Cells, Cultured

ADAM10 Protein

Cell Adhesion

Eczema - metabolism

MAP Kinase Signaling System

Transforming Growth Factor beta - pharmacology

Tumor Necrosis Factor-alpha - pharmacology

Membrane Proteins - physiology

Eczema - pathology

Blister - etiology

Cytokines - pharmacology

Interferon-gamma - pharmacology

Keratinocytes - physiology

Details

Title: Subtitle: ADAM10-mediated E-cadherin release is regulated by proinflammatory cytokines and modulates keratinocyte cohesion in eczematous dermatitis
Creators: Thorsten Maretzky - Biochemical Institute, Christian-Albrecht University Kiel, Kiel, Germany
Felix Scholz
Bente Köten
Ehrhardt Proksch
Paul Saftig
Karina Reiss
Resource Type: Journal article
Publication Details: Journal of investigative dermatology, Vol.128(7), pp.1737-1746
DOI: 10.1038/sj.jid.5701242
PMID: 18200054
ISSN: 0022-202X
eISSN: 1523-1747
Language: English
Date published: 07/2008
Academic Unit: Internal Medicine
Record Identifier: 9984094404202771

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