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The handle http://hdl.handle.net/1887/20911 holds various files of this Leiden University dissertation. Author: Janssens, Michelle Title: Atopic eczema : the role of stratum corneum lipids in the skin barrier Issue Date: 2013-05-30

Atopic eczema:

The role of stratum corneum lipids in

the skin barrier

Michelle Janssens

The investigations described in this thesis have been co-supervised by Dr. P.J. Caspers and Dr. A.P.M. Lavrijsen and were performed at the division of Drug Delivery Technology at the Leiden Academic Centre for Drug Research (LACDR), Leiden University, Leiden, The Netherlands. This research is supported by the Dutch Technology Foundation STW, which is part of the Netherlands Organisation for Scientific Research (NWO) and partly funded by the Ministry of Economic Affairs (project number 10064). In addition, the following companies provided substantial financial support to the research: Astellas, Evonik Industries, RiverD International B.V. and Unilever. The printing of this thesis was financially supported by STW. © 2013 Michelle Janssens. All rights reserved. No part of this thesis may be reproduced or transmitted in any form or by any means without written permission of the author. Cover image and formatting: Thijs van den Hoven. Printed by Proefschriftmaken.nl || Uitgeverij BOXPress

Atopic eczema:

The role of stratum corneum lipids in

the skin barrier

Proefschrift

ter verkrijging van

de graad van Doctor aan de Universiteit Leiden

op gezag van Rector Magnificus prof. mr. C.J.J.M. Stolker,

volgens besluit van het College voor Promoties

te verdedigen op donderdag 30 mei 2013

klokke 13.45 uur

door

Michelle Janssens

geboren te Roosendaal en Nispen

in 1985

Promotiecommissie

Promotor: Prof. Dr. J.A. Bouwstra

Co-promotores: Dr. P.J. Caspers

Dr. A.P.M. Lavrijsen

Overige leden: Prof. Dr. M. Danhof

Prof. Dr. W. Jiskoot

Prof. Dr. E. Proksch

Dr. A. El Ghalbzouri

Voor mijn ouders

Aan Thijs

Table of contents

8

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List of abbreviations

AE atopic eczema

ANOVA analysis of variance

APCI atmospheric pressure chemical ionization

aSMASE acid sphingomyelinase

ATR attenuated total reflectance

a.u. arbitrary unit

AUC area under the curve

BCA bicinchoninic acid

BSA bovine serum albumin

CCD charge-coupled device

CER ceramide

CERS ceramide synthase

CHOL cholesterol

ED electron diffraction

ELA2 elastase 2

ELOVL elongation of very long chain fatty acids

FEG field emission gun

FFA free fatty acid

FLG filaggrin gene

FTIR Fourier transform infrared spectroscopy

FWHM full width half maximum

hex hexagonal

HPLC high performance liquid chromatography

IS internal standard

KLK kallikrein

LB lamellar body

LC-MS liquid chromatography-mass spectrometry

LEKTI lympho-epithelial Kazal-type-related inhibitor

LPP long periodicity phase

MCT mercury-cadmium-telluride

MUFA mono-unsaturated fatty acid

NeS Netherton syndrome

NMF natural moisturizing factor

orth orthorhombic

PAR2 proteinase-activated receptor 2

PCA 2-pyrrolidone-5-carboxylic acid

PPAR peroxisome proliferator-activated receptor

S/N signal to noise ratio

SAXD small angle X-ray diffraction

SB stratum basale

SC stratum corneum

SCD stearoyl-coenzyme A desaturase

SCORAD scoring atopic dermatitis

SD standard deviation

SEM standard error of the mean

SG stratum granulosum

SPINK5 serine protease inhibitor Kazal-type 5

SPP short periodicity phase

SS stratum spinosum

TEM transmission electron microscope

TEWL transepidermal water loss

TSLP thymic stromal lymphopoietin

UCA urocanic acid

Ceramide nomenclature

AdS α-hydroxy fatty acid amide-linked to a dihydrosphingosine base

AH α-hydroxy fatty acid amide-linked to a 6-hydroxysphingosine base

AP α-hydroxy fatty acid amide-linked to a phytosphingosine base

AS α-hydroxy fatty acid amide-linked to a sphingosine base

EOdS esterified ω-hydroxy fatty acid amide-linked to a dihydrosphingosine base

EOH esterified ω-hydroxy fatty acid amide-linked to a 6-hydroxysphingosine base

EOP esterified ω-hydroxy fatty acid amide-linked to a phytosphingosine base

EOS esterified ω-hydroxy fatty acid amide-linked to a sphingosine base

NdS non-hydroxy fatty acid amide-linked to a dihydrosphingosine base

NH non-hydroxy fatty acid amide-linked to a 6-hydroxysphingosine base

NP non-hydroxy fatty acid amide-linked to a phytosphingosine base

NS non-hydroxy fatty acid amide-linked to a sphingosine base

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