Skin of atopic dermatitis patients shows disturbed β-glucocerebrosidase and acid sphingomyelinase activity that relates to changes in stratum corneum lipid composition

Daphne E. C. Boer; Jeroen van Smeden; Hanin Al-Khakany; Elizaveta Melnik; Rianne van Dijk; Samira Absalah; Rob J. Vreeken; Caroline C. P. Haenen; Adriana P. M. Lavrijsen; Herman S. Overkleeft; Johannes M. F. G. Aerts; Joke A. Bouwstra

doi:10.1016/j.bbalip.2020.158673

Skin of atopic dermatitis patients shows disturbed β-glucocerebrosidase and acid sphingomyelinase activity that relates to changes in stratum corneum lipid composition

Daphne E. C. Boer, Jeroen van Smeden, Hanin Al-Khakany, Elizaveta Melnik, Rianne van Dijk, Samira Absalah, Rob J. Vreeken, Caroline C. P. Haenen, Adriana P. M. Lavrijsen, Herman S. Overkleeft, Johannes M. F. G. Aerts, Joke A. Bouwstra^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Patients with Atopic Dermatitis (AD) suffer from inflamed skin and skin barrier defects. Proper formation of the outermost part of the skin, the stratum corneum (SC), is crucial for the skin barrier function. In this study we analyzed the localization and activity of lipid enzymes beta-glucocerebrosidase (GBA) and acid sphingomyelinase (ASM) in the skin of AD patients and controls. Localization of both the expression and activity of GBA and ASM in the epidermis of AD patients was altered, particularly at lesional skin sites. These changes aligned with the altered SC lipid composition. More specifically, abnormal localization of GBA and ASM related to an increase in specific ceramide subclasses [AS] and [NS]. Moreover we related the localization of the enzymes to the amounts of SC ceramide subclasses and free fatty acids (FFAs).

We report a correlation between altered localization of active GBA and ASM and a disturbed SC lipid composition. Localization of antimicrobial peptide beta-defensin-3 (HBD-3) and AD biomarker Thymus and Activation Regulated Chemokine (TARC) also appeared to be diverging in AD skin compared to control. This research highlights the relation between correct localization of expressed and active lipid enzymes and a normal SC lipid composition for a proper skin barrier.

Original language	English
Article number	158673
Number of pages	10
Journal	Biochimica et Biophysica Acta-Molecular and Cell Biology of Lipids
Volume	1865
Issue number	6
DOIs	https://doi.org/10.1016/j.bbalip.2020.158673
Publication status	Published - Jun 2020

Keywords

Atopic dermatitis
Stratum corneum
Glucocerebrosidase
Acid sphingomyelinase
Mass spectrometry
Fluorescence microscopy
ACTIVATION-REGULATED CHEMOKINE
IN-SITU VISUALIZATION
BARRIER FUNCTION
SERUM THYMUS
FILAGGRIN
ORGANIZATION
MAINTENANCE
PRECURSORS
BIOMARKERS
CHILDREN

Access to Document

10.1016/j.bbalip.2020.158673Licence: CC BY-NC-ND

Cite this

Boer, D. E. C., van Smeden, J., Al-Khakany, H., Melnik, E., van Dijk, R., Absalah, S., Vreeken, R. J., Haenen, C. C. P., Lavrijsen, A. P. M., Overkleeft, H. S., Aerts, J. M. F. G., & Bouwstra, J. A. (2020). Skin of atopic dermatitis patients shows disturbed β-glucocerebrosidase and acid sphingomyelinase activity that relates to changes in stratum corneum lipid composition. Biochimica et Biophysica Acta-Molecular and Cell Biology of Lipids, 1865(6), Article 158673. https://doi.org/10.1016/j.bbalip.2020.158673

@article{79dde371c3314f849d8b4025363e1de8,

title = "Skin of atopic dermatitis patients shows disturbed β-glucocerebrosidase and acid sphingomyelinase activity that relates to changes in stratum corneum lipid composition",

abstract = "Patients with Atopic Dermatitis (AD) suffer from inflamed skin and skin barrier defects. Proper formation of the outermost part of the skin, the stratum corneum (SC), is crucial for the skin barrier function. In this study we analyzed the localization and activity of lipid enzymes beta-glucocerebrosidase (GBA) and acid sphingomyelinase (ASM) in the skin of AD patients and controls. Localization of both the expression and activity of GBA and ASM in the epidermis of AD patients was altered, particularly at lesional skin sites. These changes aligned with the altered SC lipid composition. More specifically, abnormal localization of GBA and ASM related to an increase in specific ceramide subclasses [AS] and [NS]. Moreover we related the localization of the enzymes to the amounts of SC ceramide subclasses and free fatty acids (FFAs).We report a correlation between altered localization of active GBA and ASM and a disturbed SC lipid composition. Localization of antimicrobial peptide beta-defensin-3 (HBD-3) and AD biomarker Thymus and Activation Regulated Chemokine (TARC) also appeared to be diverging in AD skin compared to control. This research highlights the relation between correct localization of expressed and active lipid enzymes and a normal SC lipid composition for a proper skin barrier.",

keywords = "Atopic dermatitis, Stratum corneum, Glucocerebrosidase, Acid sphingomyelinase, Mass spectrometry, Fluorescence microscopy, ACTIVATION-REGULATED CHEMOKINE, IN-SITU VISUALIZATION, BARRIER FUNCTION, SERUM THYMUS, FILAGGRIN, ORGANIZATION, MAINTENANCE, PRECURSORS, BIOMARKERS, CHILDREN",

author = "Boer, {Daphne E. C.} and {van Smeden}, Jeroen and Hanin Al-Khakany and Elizaveta Melnik and {van Dijk}, Rianne and Samira Absalah and Vreeken, {Rob J.} and Haenen, {Caroline C. P.} and Lavrijsen, {Adriana P. M.} and Overkleeft, {Herman S.} and Aerts, {Johannes M. F. G.} and Bouwstra, {Joke A.}",

note = "Publisher Copyright: {\textcopyright} 2020 The Author(s)",

year = "2020",

month = jun,

doi = "10.1016/j.bbalip.2020.158673",

language = "English",

volume = "1865",

journal = "Biochimica et Biophysica Acta-Molecular and Cell Biology of Lipids",

issn = "1388-1981",

publisher = "Elsevier",

number = "6",

}

Boer, DEC, van Smeden, J, Al-Khakany, H, Melnik, E, van Dijk, R, Absalah, S, Vreeken, RJ, Haenen, CCP, Lavrijsen, APM, Overkleeft, HS, Aerts, JMFG & Bouwstra, JA 2020, 'Skin of atopic dermatitis patients shows disturbed β-glucocerebrosidase and acid sphingomyelinase activity that relates to changes in stratum corneum lipid composition', Biochimica et Biophysica Acta-Molecular and Cell Biology of Lipids, vol. 1865, no. 6, 158673. https://doi.org/10.1016/j.bbalip.2020.158673

Skin of atopic dermatitis patients shows disturbed β-glucocerebrosidase and acid sphingomyelinase activity that relates to changes in stratum corneum lipid composition. / Boer, Daphne E. C.; van Smeden, Jeroen; Al-Khakany, Hanin et al.
In: Biochimica et Biophysica Acta-Molecular and Cell Biology of Lipids, Vol. 1865, No. 6, 158673, 06.2020.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Skin of atopic dermatitis patients shows disturbed β-glucocerebrosidase and acid sphingomyelinase activity that relates to changes in stratum corneum lipid composition

AU - Boer, Daphne E. C.

AU - van Smeden, Jeroen

AU - Al-Khakany, Hanin

AU - Melnik, Elizaveta

AU - van Dijk, Rianne

AU - Absalah, Samira

AU - Vreeken, Rob J.

AU - Haenen, Caroline C. P.

AU - Lavrijsen, Adriana P. M.

AU - Overkleeft, Herman S.

AU - Aerts, Johannes M. F. G.

AU - Bouwstra, Joke A.

PY - 2020/6

Y1 - 2020/6

N2 - Patients with Atopic Dermatitis (AD) suffer from inflamed skin and skin barrier defects. Proper formation of the outermost part of the skin, the stratum corneum (SC), is crucial for the skin barrier function. In this study we analyzed the localization and activity of lipid enzymes beta-glucocerebrosidase (GBA) and acid sphingomyelinase (ASM) in the skin of AD patients and controls. Localization of both the expression and activity of GBA and ASM in the epidermis of AD patients was altered, particularly at lesional skin sites. These changes aligned with the altered SC lipid composition. More specifically, abnormal localization of GBA and ASM related to an increase in specific ceramide subclasses [AS] and [NS]. Moreover we related the localization of the enzymes to the amounts of SC ceramide subclasses and free fatty acids (FFAs).We report a correlation between altered localization of active GBA and ASM and a disturbed SC lipid composition. Localization of antimicrobial peptide beta-defensin-3 (HBD-3) and AD biomarker Thymus and Activation Regulated Chemokine (TARC) also appeared to be diverging in AD skin compared to control. This research highlights the relation between correct localization of expressed and active lipid enzymes and a normal SC lipid composition for a proper skin barrier.

AB - Patients with Atopic Dermatitis (AD) suffer from inflamed skin and skin barrier defects. Proper formation of the outermost part of the skin, the stratum corneum (SC), is crucial for the skin barrier function. In this study we analyzed the localization and activity of lipid enzymes beta-glucocerebrosidase (GBA) and acid sphingomyelinase (ASM) in the skin of AD patients and controls. Localization of both the expression and activity of GBA and ASM in the epidermis of AD patients was altered, particularly at lesional skin sites. These changes aligned with the altered SC lipid composition. More specifically, abnormal localization of GBA and ASM related to an increase in specific ceramide subclasses [AS] and [NS]. Moreover we related the localization of the enzymes to the amounts of SC ceramide subclasses and free fatty acids (FFAs).We report a correlation between altered localization of active GBA and ASM and a disturbed SC lipid composition. Localization of antimicrobial peptide beta-defensin-3 (HBD-3) and AD biomarker Thymus and Activation Regulated Chemokine (TARC) also appeared to be diverging in AD skin compared to control. This research highlights the relation between correct localization of expressed and active lipid enzymes and a normal SC lipid composition for a proper skin barrier.

KW - Atopic dermatitis

KW - Stratum corneum

KW - Glucocerebrosidase

KW - Acid sphingomyelinase

KW - Mass spectrometry

KW - Fluorescence microscopy

KW - ACTIVATION-REGULATED CHEMOKINE

KW - IN-SITU VISUALIZATION

KW - BARRIER FUNCTION

KW - SERUM THYMUS

KW - FILAGGRIN

KW - ORGANIZATION

KW - MAINTENANCE

KW - PRECURSORS

KW - BIOMARKERS

KW - CHILDREN

U2 - 10.1016/j.bbalip.2020.158673

DO - 10.1016/j.bbalip.2020.158673

M3 - Article

C2 - 32092464

SN - 1388-1981

VL - 1865

JO - Biochimica et Biophysica Acta-Molecular and Cell Biology of Lipids

JF - Biochimica et Biophysica Acta-Molecular and Cell Biology of Lipids

IS - 6

M1 - 158673

ER -

Boer DEC, van Smeden J, Al-Khakany H, Melnik E, van Dijk R, Absalah S et al. Skin of atopic dermatitis patients shows disturbed β-glucocerebrosidase and acid sphingomyelinase activity that relates to changes in stratum corneum lipid composition. Biochimica et Biophysica Acta-Molecular and Cell Biology of Lipids. 2020 Jun;1865(6):158673. doi: 10.1016/j.bbalip.2020.158673