Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Dermatology
Published in: BMC Dermatology 1/2020

01-12-2020 | Atopic Dermatitis | Research article

The ceramide [NP]/[NS] ratio in the stratum corneum is a potential marker for skin properties and epidermal differentiation

Authors: Urara Yokose, Junko Ishikawa, Yuki Morokuma, Ayano Naoe, Yosuke Inoue, Yuka Yasuda, Hisashi Tsujimura, Tsutomu Fujimura, Takatoshi Murase, Atsushi Hatamochi

Published in: BMC Dermatology | Issue 1/2020

Login to get access

Abstract

Background

Specific species of ceramides (Cer), major constituents of lipids in the stratum corneum (SC), are decreased and are correlated with SC barrier and water-holding functions in the skin of patients with atopic dermatitis (AD) or psoriasis (Pso). However, possible correlations between Cer subclass ratios and skin properties in barrier-disrupted skin and in healthy skin remain unclear. The objective of this study was to identify a new marker to evaluate skin properties and epidermal differentiation in SC not only in barrier-disrupted skin but also in healthy skin.

Methods

The Cer subclass ratios in the SC of healthy control subjects and in patients with AD or Pso were evaluated. Correlations with candidate markers and facial skin features of healthy Japanese females (20–74 years old, n = 210) were investigated. Variations of markers during epidermal differentiation were studied in human epidermis and in cultured keratinocytes.

Results

The ratios of Cer [NP]/[NS], Cer [NH]/[NS], Cer [NP]/[AS], Cer [NH]/[NS], Cer [NDS]/[AS], Cer [AH]/[AS] and Cer [EOP]/[AS] showed significant differences between non-lesional skin of AD patients and normal skin of healthy control subjects, as well as Pso patients and their healthy control subjects. The Cer [NP]/[NS] ratio was correlated with SC functional parameters (transepidermal water loss and capacitance) and with skin appearance (texture, scaling and color) even in the cheek skin of healthy female subjects. The Cer [NP]/[NS] ratio in the SC was approximately 18-times higher than in living keratinocytes, and it increased as they differentiated.

Conclusions

The Cer [NP]/[NS] ratio in the SC is a potential marker for skin properties and epidermal differentiation in barrier-disrupted skin as well as in healthy skin.
Appendix
Available only for authorised users
Literature
1.
Elias PM. Epidermal lipids, barrier function, and desquamation. J Invest Dermatol. 1983;80:44s–9s.PubMedCrossRef
2.
Proksch E, Holleran WM, Menon GK, Elias PM, Feingold KR. Barrier function regulates epidermal lipid and DNA synthesis. Br J Dermatol. 1993;128:473–82.PubMedCrossRef
3.
Breiden B, Sandhoff K. The role of sphingolipid metabolism in cutaneous permeability barrier formation. Biochim Biophys Acta. 2014;1841:441–52.PubMedCrossRef
4.
van Smeden J, Hoppel L, van der Heijden R, Hankemeier T, Vreeken RJ, Bouwstra JA. LC/MS analysis of stratum corneum lipids: ceramide profiling and discovery. J Lipid Res. 2011;52:1211–21.PubMedPubMedCentralCrossRef
5.
Motta S, Monti M, Sesana S, Caputo R, Carelli S, Ghidoni R. Ceramide composition of the psoriatic scale. Biochim Biophys Acta. 1993;1182:147–51.PubMedCrossRef
6.
Masukawa Y, Narita H, Shimizu E, Kondo N, Sugai Y, Oba T, et al. Characterization of overall ceramide species in human stratum corneum. J Lipid Res. 2008;49:1466–76.PubMedCrossRef
7.
Jia ZX, Zhang JL, Shen CP, Ma L. Profile and quantification of human stratum corneum ceramides by normal-phase liquid chromatography coupled with dynamic multiple reaction monitoring of mass spectrometry: development of targeted lipidomic method and application to human stratum corneum of different age groups. Anal Bioanal Chem. 2016;408:6623–36.PubMedCrossRef
8.
Ishikawa J, Narita H, Kondo N, Hotta M, Takagi Y, Masukawa Y, et al. Changes in the ceramide profile of atopic dermatitis patients. J Invest Dermatol. 2010;130:2511–4.PubMedCrossRef
9.
Koyano S, Hatamochi A, Yamazaki S, Ishikawa J, Kitahara T, Narita H, et al. Psoriasis patients have abnormal ceramide profile in stratum corneum. Nishinihon J Dermatol. 2010;72:494–9.CrossRef
10.
Imokawa G, Abe A, Jin K, Higaki Y, Kawashima M, Hidano A. Decreased level of ceramides in stratum corneum of atopic dermatitis: an etiologic factor in atopic dry skin? J Invest Dermatol. 1991;96:523–6.PubMedCrossRef
11.
Di Nardo A, Wertz P, Giannetti A, Seidenari S. Ceramide and cholesterol composition of the skin of patients with atopic dermatitis. Acta Derm Venereol. 1998;78:27–30.PubMedCrossRef
12.
Farwanah H, Raith K, Neubert RH, Wohlrab J. Ceramide profiles of the uninvolved skin in atopic dermatitis and psoriasis are comparable to those of healthy skin. Arch Dermatol Res. 2005;296:514–21.PubMedCrossRef
13.
Groen D, Poole DS, Gooris GS, Bouwstra JA. Investigating the barrier function of skin lipid models with varying compositions. Eur J Pharm Biopharm. 2011;79:334–42.PubMedCrossRef
14.
Bouwstra JA, Gooris GS. The lipid organisation in human stratum corneum and model systems. Open Dermatol J. 2010;4:10–3.
15.
Janssens M, van Smeden J, Puppels GJ, Lavrijsen AP, Caspers PJ, Bouwstra JA. Lipid to protein ratio plays an important role in the skin barrier function in patients with atopic eczema. Br J Dermatol. 2014;170:1248–55.PubMedCrossRef
16.
Joo KM, Hwang JH, Bae S, Nahm DH, Park HS, Ye YM, et al. Relationship of ceramide-, and free fatty acid-cholesterol ratios in the stratum corneum with skin barrier function of normal, atopic dermatitis lesional and non-lesional skins. J Dermatol Sci. 2015;77:71–4.PubMedCrossRef
17.
Ishikawa J, Shimotoyodome Y, Ito S, Miyauchi Y, Fujimura T, Kitahara T, et al. Variations in the ceramide profile in different seasons and regions of the body contribute to stratum corneum functions. Arch Dermatol Res. 2013;305:151–62.PubMedCrossRef
18.
Ishikawa J, Yoshida H, Ito S, Naoe A, Fujimura T, Kitahara T, et al. Dry skin in the winter is related to the ceramide profile in the stratum corneum and can be improved by treatment with a Eucalyptus extract. J Cosmet Dermatol. 2013;12:3–11.PubMedCrossRef
19.
Mutanu Jungersted J, Hellgren LI, Høgh JK, Drachmann T, Jemec GB, Agner T. Ceramides and barrier function in healthy skin. Acta Derm Venereol. 2010;90:350–3.PubMedCrossRef
20.
Masukawa Y, Narita H, Sato H, Naoe A, Kondo N, Sugai Y, et al. Comprehensive quantification of ceramide species in human stratum corneum. J Lipid Res. 2009;50:1708–19.PubMedPubMedCentralCrossRef
21.
Ohno Y, Nakamichi S, Ohkuni A, Kamiyama N, Naoe A, Tsujimura H, et al. Essential role of the cytochrome P450 CYP4F22 in the production of acylceramide, the key lipid for skin permeability barrier formation. Proc Natl Acad Sci U S A. 2015;112:7707–12.PubMedPubMedCentralCrossRef
22.
Bligh EG, Dyer WJ. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959;37:911–7.PubMedCrossRef
23.
Ekanayake-Mudiyanselage S, Aschauer H, Schmook FP, Jensen JM, Meingassner JG, Proksch E. Expression of epidermal keratins and the cornified envelope protein involucrin is influenced by permeability barrier disruption. J Invest Dermatol. 1998;111:517–23.PubMedCrossRef
24.
Kunii T, Hirao T, Kikuchi K, Tagami H. Stratum corneum lipid profile and maturation pattern of corneocytes in the outermost layer of fresh scars: the presence of immature corneocytes plays a much more important role in the barrier dysfunction than do changes in intercellular lipids. Br J Dermatol. 2003;149:749–56.PubMedCrossRef
25.
Jensen JM, Pfeiffer S, Akaki T, Schröder JM, Kleine M, Neumann C, et al. Barrier function, epidermal differentiation, and human beta-defensin 2 expression in tinea corporis. J Invest Dermatol. 2007;127:1720–7.PubMedCrossRef
26.
Kim D, Lee NR, Park SY, Jun M. K. Lee, S. Kim, et al. as in atopic dermatitis, nonlesional skin in allergic contact dermatitis displays abnormalities in barrier function and ceramide content. J Invest Dermatol. 2017;137:748–50.PubMedCrossRef
27.
Danso MO, van Drongelen V, Mulder A, van Esch J, Scott H, van Smeden J, et al. TNF-alpha and Th2 cytokines induce atopic dermatitis-like features on epidermal differentiation proteins and stratum corneum lipids in human skin equivalents. J Invest Dermatol. 2014;134:1941–50.PubMedCrossRef
28.
Pierard GE. EEMCO guidance for the assessment of skin colour. J Eur Acad Dermatol Venereol. 1998;10:1–11.PubMed
29.
Jiang ZX, DeLaCruz J. Appearance benefits of skin moisturization. Skin Res Technol. 2011;17:51–5.PubMedCrossRef
30.
31.
Briot A, Deraison C, Lacroix M, Bonnart C, Robin A, Besson C, et al. Kallikrein 5 induces atopic dermatitis-like lesions through PAR2-mediated thymic stromal lymphopoietin expression in Netherton syndrome. J Exp Med. 2009;206:1135–47.PubMedPubMedCentralCrossRef
32.
Oyoshi MK, He R, Kumar L, Yoon J, Geha RS. Cellular and molecular mechanisms in atopic dermatitis. Adv Immunol. 2009;102:135–226.PubMedCrossRef
33.
Sawada E, Yoshida N, Sugiura A, Imokawa G. 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. J Dermatol Sci. 2012;68:25–35.PubMedCrossRef
34.
Yoshida N, Sawada E, Imokawa G. A reconstructed human epidermal keratinization culture model to characterize ceramide metabolism in the stratum corneum. Arch Dermatol Res. 2012;304:563–77.PubMedCrossRef
35.
t'Kindt R, Jorge L, Dumont E, Couturon P, David F, Sandra P, et al. Profiling and characterizing skin ceramides using reversed-phase liquid chromatography-quadrupole time-of-flight mass spectrometry. Anal Chem. 2012;84:403–11.PubMedCrossRef
36.
Bachelor M, Binder RL, Cambron RT, Kaczvinsky JR, Spruell R, Wehmeyer KR, et al. Transcriptional profiling of epidermal barrier formation in vitro. J Dermatol Sci. 2014;73:187–97.PubMedCrossRef
37.
Omae F, Miyazaki M, Enomoto A, Suzuki M, Suzuki Y, Suzuki A. DES2 protein is responsible for phytoceramide biosynthesis in the mouse small intestine. Biochem J. 2004;379:687–95.PubMedPubMedCentralCrossRef
38.
Mizutani Y, Mitsutake S, Tsuji K, Kihara A, Igarashi Y. Ceramide biosynthesis in keratinocyte and its role in skin function. Biochimie. 2009;91:784–90.PubMedCrossRef
39.
Mizutani Y, Kihara A, Igarashi Y. Identification of the human sphingolipid C4-hydroxylase, hDES2, and its up-regulation during keratinocyte differentiation. FEBS Lett. 2004;563:93–7.PubMedCrossRef
40.
Mao C, Obeid LM. Ceramidases: regulators of cellular responses mediated by ceramide, sphingosine, and sphingosine-1-phosphate. Biochim Biophys Acta. 1781;2008:424–34.
41.
Sun W, Xu R, Hu W, Jin J, Crellin HA, Bielawski J, et al. Upregulation of the human alkaline ceramidase 1 and acid ceramidase mediates calcium-induced differentiation of epidermal keratinocytes. J Invest Dermatol. 2008;128:389–97.PubMedCrossRef
Metadata
Title
The ceramide [NP]/[NS] ratio in the stratum corneum is a potential marker for skin properties and epidermal differentiation
Authors
Urara Yokose
Junko Ishikawa
Yuki Morokuma
Ayano Naoe
Yosuke Inoue
Yuka Yasuda
Hisashi Tsujimura
Tsutomu Fujimura
Takatoshi Murase
Atsushi Hatamochi
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Dermatology / Issue 1/2020
Electronic ISSN: 1471-5945
DOI
https://doi.org/10.1186/s12895-020-00102-1

Other articles of this Issue 1/2020

BMC Dermatology 1/2020 Go to the issue

Case report

Madurella mycetomatis infection of the foot: a case report of a neglected tropical disease in a non-endemic region

Research article

Prevalence of pressure ulcers among hospitalized adult patients in Ethiopia: a systematic review and meta-analysis

Research article

A translation and preliminary validation of the Dutch Wound-QoL questionnaire

Research article

Weight gain in patients with severe atopic dermatitis treated with dupilumab: a cohort study

Research article

Diaper rashes can indicate systemic conditions other than diaper dermatitis

Research article

Associations of self-reported atopic dermatitis with comorbid conditions in adults: a population-based cross-sectional study