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Cited by 309Dermatology and Skin DiseasesSphingolipid Metabolism and SignalingAdvancements in Transdermal Drug Delivery

Impaired sphingomyelinase activity and epidermal differentiation in atopic dermatitis

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Jensen, Jens-Michael, Fölster-Holst, Regina, Baranowsky, Anke, Schunck, Michael, Winoto-Morbach, Supandi, Neumann, Claudia, Schütze, Stefan, Proksch, Ehrhardt·2004·Journal of Investigative Dermatology
DOI 10.1111/j.0022-202x.2004.22621.x
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Abstract

A defective permeability barrier leads to the penetration of environmental allergens into the skin and initiates immunological reactions and inflammation crucially involved in the pathogenesis of atopic dermatitis (AD). Decreased stratum corneum ceramide content may cause the defect in permeability barrier function consistently found in AD. Acid and neutral sphingomyelinase (A- and N-SMase) generate ceramides with structural and signal transduction functions in epidermal proliferation and differentiation. We determined epidermal SMase activities, DNA synthesis, involucrin, loricrin, filaggrin, and keratin expression in lesional and non-lesional skin of AD patients. We found decreased epidermal A-SMase activity in lesional and non-lesional skin, correlating with reduced stratum corneum ceramide content and disturbed barrier function. N-SMase activity was reduced in non-lesional skin and more significantly reduced in lesional skin, correlating with impaired expression of cornified envelope proteins and keratins, important for skin barrier function. Changes in involucrin, loricrin, filaggrin, keratin K 5 (basal) and K 16 (proliferation associated) were noticed in non-lesional and lesional skin, whereas changes in K 10 (suprabasal), K 6 (proliferation associated), and K 17 (inflammation associated) were found only in lesional skin. In summary, reduction in SMase-generating ceramides and impaired differentiation are involved in the defective barrier function found in AD.

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  • FLG and LOR expression levels are reduced in lesional and non-lesional skin in atopic dermatitis.

    “Atopic dry skin is associated with a marked reduction of skin barrier proteins, such as filaggrin (FLG) and loricrin (LOR).”

    From Antioxidant Artemisia princeps Extract Enhances the Expression of Filaggrin and Loricrin via the AHR/OVOL1 Pathway (2017) · cites this paper as [12]

    The Results (Figure 3; page unavailable) report significantly reduced filaggrin staining in both non-lesional and lesional atopic skin. But the Results (Figure 4; page unavailable) report increased, not reduced, loricrin levels in both. Thus the claim is supported for FLG but contradicted for LOR. (LLM, conf=0.90)

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  • Skin inflammation decreases FLG and LOR expression and disrupts epidermal barrier function; barrier dysfunction augments skin inflammation.

    “Skin inflammation decreases FLG and LOR expression and disrupts epidermal barrier function; moreover, in the opposite direction, barrier dysfunction augments skin inflammation [12,13,26].”

    From Antioxidant Artemisia princeps Extract Enhances the Expression of Filaggrin and Loricrin via the AHR/OVOL1 Pathway (2017) · cites this paper as [12]

    The Discussion reports reduced filaggrin in atopic skin, and the passage labeled Abstract describes barrier disruption promoting eczematous dermatitis. But the Results and Discussion report increased—not decreased—loricrin in both lesional and non-lesional atopic skin. The paper also does not establish that inflammation caused the observed expression changes. (LLM, conf=0.88)

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Authors
Jensen, J.-M., Fölster-Holst, R., Baranowsky, A., Schunck, M., Winoto-Morbach, S., Neumann, C., Schütze, S., & Proksch, E.
Affiliations
Christian-Albrechts-Universität zu Kiel (DE)
Corresponding author
Proksch, Ehrhardt
ORCID
Venue
Journal of Investigative Dermatology
Publisher
Elsevier BV
Published
2004-06
Volume
122
Issue
6
Pages
1423-1431
ISSN
0022-202X (ISSN-L)
DOI
10.1111/j.0022-202x.2004.22621.x
OpenAlex
W2077796802
Cited by
309
References
83
Citations by year
2026: 1 · 2025: 1 · 2024: 13 · 2023: 12 · 2022: 13 · 2021: 16 · 2020: 18 · 2019: 12 · 2018: 11 · 2017: 16 · 2016: 15 · 2015: 13 · 2014: 23 · 2013: 19 · 2012: 24
FWCI
15.28
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Investigative Dermatology (publishedVersion)
  • PubMed (publishedVersion)
Funders
Deutsche Forschungsgemeinschaft (SFB 415)
Topics
  • Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advancements in Transdermal Drug Delivery
Keywords
atopic dermatitis, sphingomyelinase, acid sphingomyelinase, neutral sphingomyelinase, ceramide, stratum corneum, skin barrier function, epidermal differentiation, involucrin, loricrin, filaggrin, keratin, DNA synthesis, lesional skin
MeSH terms
Filaggrin Proteins, Cell Differentiation, Cell Division, Ceramides, Dermatitis, Atopic, Epidermis, Female, Humans, Intermediate Filament Proteins, Keratins, Male, Membrane Proteins, Protein Precursors, Sphingomyelin Phosphodiesterase, Substrate Specificity, Water, Blotting, Western, Signal Transduction, Biomarkers

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