Cited by 488Dermatology and Skin DiseasesAdvancements in Transdermal Drug DeliveryContact Dermatitis and Allergies

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Increase in short-chain ceramides correlates with an altered lipid organization and decreased barrier function in atopic eczema patients

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Janssens, Michelle, van Smeden, Jeroen, Gooris, Gert S., Bras, Wim, Portale, Guiseppe, Caspers, Peter J., Vreeken, Rob J., Hankemeier, Thomas, Kezic, Sanja, Wolterbeek, Ron, Lavrijsen, Adriana P., Bouwstra, Joke A.·2012·Journal of Lipid Research

DOI 10.1194/jlr.p030338PMC PMC3494247

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Abstract

A hallmark of atopic eczema (AE) is skin barrier dysfunction. Lipids in the stratum corneum (SC), primarily ceramides, fatty acids, and cholesterol, are crucial for the barrier function, but their role in relation to AE is indistinct. Filaggrin is an epithelial barrier protein with a central role in the pathogenesis of AE. Nevertheless, the precise causes of AE-associated barrier dysfunction are largely unknown. In this study, a comprehensive analysis of ceramide composition and lipid organization in nonlesional SC of AE patients and control subjects was performed by means of mass spectrometry, infrared spectroscopy, and X-ray diffraction. In addition, the skin barrier and clinical state of the disease were examined. The level of ceramides with an extreme short chain length is drastically increased in SC of AE patients, which leads to an aberrant lipid organization and a decreased skin barrier function. Changes in SC lipid properties correlate with disease severity but are independent of filaggrin mutations. We demonstrate for the first time that changes in ceramide chain length and lipid organization are directly correlated with the skin barrier defects in nonlesional skin of AE patients. We envisage that these insights will provide a new therapeutic entry in therapy and prevention of AE.

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Self-citation
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“rier defect, is characterized by reduced ordering of SC lipids determined using the same technique employed here (15, 16).”
Method
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Self-citation
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Self-citation
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Self-citation
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Self-citation

Authors: Janssens, M., van Smeden, J., Gooris, G. S., Bras, W., Portale, G., Caspers, P. J., Vreeken, R. J., Hankemeier, T., Kezic, S., Wolterbeek, R., Lavrijsen, A. P., & Bouwstra, J. A.
Affiliations: Leiden University (NL)
Dutch Research Council (NL)
Erasmus MC (NL)
Leiden University Medical Center (NL)
Corresponding author: Bouwstra, Joke A.
ORCID: van Smeden, Jeroen
Bras, Wim
Caspers, Peter J.
Vreeken, Rob J.
Hankemeier, Thomas
Bouwstra, Joke A.
Venue: Journal of Lipid Research
Publisher: Elsevier BV
Published: 2012-12
Volume: 53
Issue: 12
Pages: 2755-2766
ISSN: 0022-2275 (ISSN-L)
DOI: 10.1194/jlr.p030338
PMC: PMC3494247
OpenAlex: W2130942098
Cited by: 488
References: 75
Citations by year: 2026: 31 · 2025: 37 · 2024: 47 · 2023: 30 · 2022: 36 · 2021: 42 · 2020: 39 · 2019: 41 · 2018: 37 · 2017: 32 · 2016: 32 · 2015: 28 · 2014: 33 · 2013: 20
FWCI: 32.43
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 2870 d)
Locations: Journal of Lipid Research (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
Leiden Repository (Leiden University) (submittedVersion)
Data Archiving and Networked Services (DANS) (submittedVersion)
EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Pure Amsterdam UMC (submittedVersion)
Funders: Nederlandse Organisatie voor Wetenschappelijk Onderzoek
H2020 European Research Council
Topics: Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advancements in Transdermal Drug Delivery
Health Sciences › Medicine › Dermatology › Contact Dermatitis and Allergies
Keywords: atopic dermatitis, short-chain ceramides, skin barrier dysfunction, stratum corneum lipids, lipid organization, filaggrin, non-lesional skin, disease severity
MeSH terms: Filaggrin Proteins, Adult, Ceramides, Dermatitis, Atopic, Female, Genotype, Humans, Intermediate Filament Proteins, Male, Mutation, Molecular Structure, Lipid Metabolism

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Increase in short-chain ceramides correlates with an altered lipid organization and decreased barrier function in atopic eczema patients

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