Th1 cytokines accentuate but Th2 cytokines attenuate ceramide production in the stratum corneum of human epidermal equivalents: an implication for the disrupted barrier mechanism in atopic dermatitis
Abstract
Background Although the mechanism(s) involved in the ceramide deficiency in the stratum corneum (SC) of atopic dermatitis (AD) skin is unknown, Th2 type cytokines have been reported to down-regulate ceramide levels in the epidermis. However, almost all research to date has focused on ceramide levels in the whole epidermis, not just in the SC layers alone, which are predominantly responsible for the skin barrier function. Objective We highlighted the effects of Th1/Th2 cytokines on ceramide levels in the SC. Methods We developed a modified system of human epidermal equivalents in which epidermis without a SC is cultured for 1 week to generate complete SC layers after which ceramides are extracted from the separated SC layers and are then quantified as per SC protein. Results The addition of Th2 cytokines (IL-4/IL-6) at a concentration of 10nM resulted in a marked decrease in SC ceramide levels. The reduced ceramide content in the SC was accompanied by the down-regulated expression of the genes encoding serine-palmitoyl transferase-2, acid sphingomyelinase and β-glucocerebrosidase in the epidermis. In contrast, the addition of Th1 cytokines (GM-CSF/IFN-γ/TNF-α) at concentrations of 2.5 or 10nM resulted in a slight increase in SC ceramide levels, which were accompanied by no change or an increase in the expression of those genes encoding sphingolipid metabolic enzymes in the epidermis. Conclusion These findings suggest that the Th2 type of inflammation evoked in AD skin is one o…
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The deficit in the skin barrier in AD is an important component of allergic sensitization in these patients, and also a relevant factor in disease exacerbations.
“In general, the deficit in the skin barrier in AD is an important component of allergic sensitization in these patients, and also a relevant factor in disease exacerbations.”
From Update on the pathogenesis of atopic dermatitis. (2024) · cites this paper as [57]
In cases with controlled disease (i.e., with subclinical inflammation), exposure to irritants, dust, detergents, and hot baths/showers in winter are elements recognized as triggers of clinical recurrence.
“In cases with controlled disease (i.e., with subclinical inflammation), exposure to irritants, dust, detergents, and hot baths/showers in winter are elements recognized as triggers of clinical recurrence, which reinforces the importance of maintaining therapies aimed at recovering the skin barrier and proactive strategies to prolong AD clinical remission.”
From Update on the pathogenesis of atopic dermatitis. (2024) · cites this paper as [57]
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- Authors
- Sawada, E., Yoshida, N., Sugiura, A., & Imokawa, G.
- Affiliations
- Tokyo University of Technology (JP)
- Corresponding author
- Imokawa, Genji
- Venue
- Journal of Dermatological Science
- Publisher
- Elsevier BV
- Published
- 2012-10
- Volume
- 68
- Issue
- 1
- Pages
- 25-35
- ISSN
- 0923-1811 (ISSN-L)
- OpenAlex
- W2056800957
- Cited by
- 95
- References
- 3
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 8 · 2023: 8 · 2022: 6 · 2021: 5 · 2020: 7 · 2019: 5 · 2018: 10 · 2017: 8 · 2016: 4 · 2015: 5 · 2014: 11 · 2013: 8 · 2012: 1
- FWCI
- 10.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Dermatological Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Health Sciences › Medicine › Dermatology › Contact Dermatitis and Allergies
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advancements in Transdermal Drug Delivery
- Keywords
- atopic dermatitis, ceramide, stratum corneum, Th1 cytokines, Th2 cytokines, skin barrier function, IL-4, interleukin-6, GM-CSF, interferon-gamma, TNF-α, acid sphingomyelinase, beta-glucocerebrosidase, sphingolipid metabolism, skin inflammation
- MeSH terms
- Cells, Cultured, Ceramides, Dermatitis, Atopic, Epidermis, Glucosylceramidase, Humans, Recombinant Proteins, Sphingomyelin Phosphodiesterase, Time Factors, Down-Regulation, Keratinocytes, Gene Expression Regulation, Enzymologic, Cytokines, Th1 Cells, Th2 Cells, Serine C-Palmitoyltransferase
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