Transcriptomic and lipidomic profiling of eicosanoid/docosanoid signalling in affected and non-affected skin of human atopic dermatitis patients

D. Törőcsik, Christin Weise, Janine Gericke, A. Szegedi, Renata Lucas, Johanna Mihaly, Margitta Worm, Ralph Rühl

Research output: Article

2 Citations (Scopus)

Abstract

Lipoxygenases (LOX) and cyclooxygenase (COX) are the main enzymes for PUFA metabolism to highly bio-active prostaglandins, leukotrienes, thromboxanes, lipoxins, resolvins and protectins. LOX and COX pathways are important for the regulation of pro-inflammatory or pro-resolving metabolite synthesis and metabolism for various inflammatory diseases such as atopic dermatitis (AD). In this study, we determined PUFAs and PUFA metabolites in serum as well as affected and non-affected skin samples from AD patients and the dermal expression of various enzymes, binding proteins and receptors involved in these LOX and COX pathways. Decreased EPA and DHA levels in serum and reduced EPA level in affected and non-affected skin were found; in addition, n3/n6-PUFA ratios were lower in affected and non-affected skin and serum. Mono-hydroxylated PUFA metabolites of AA, EPA, DHA and the sum of AA, EPA and DHA metabolites were increased in affected and non-affected skin. COX1 and ALOX12B expression, COX and 12/15-LOX metabolites as well as various lipids, which are known to induce itch (12-HETE, LTB4, TXB2, PGE2 and PGF2) and the ratio of pro-inflammatory vs pro-resolving lipid mediators in non-affected and affected skin as well as in the serum of AD patients were increased, while n3/n6-PUFAs and metabolite ratios were lower in non-affected and affected AD skin. Expression of COX1 and COX-metabolites was even higher in non-affected AD skin. To conclude, 12/15-LOX and COX pathways were mainly upregulated, while n3/n6-PUFA and metabolite ratios were lower in AD patients skin. All these parameters are a hallmark of a pro-inflammatory and non-resolving environment in affected and partly in non-affected skin of AD patients.

Original languageEnglish
Pages (from-to)177-189
Number of pages13
JournalExperimental Dermatology
Volume28
Issue number2
DOIs
Publication statusPublished - febr. 1 2019

Fingerprint

Eicosanoids
Atopic Dermatitis
Metabolites
Skin
Prostaglandin-Endoperoxide Synthases
Lipoxygenases
Omega-3 Fatty Acids
Metabolism
Serum
CD59 Antigens
12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
Lipoxins
Lipids
Dinoprost
Leukotriene B4
Leukotrienes
Thromboxanes
Enzymes
Dinoprostone
Prostaglandins

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology

Cite this

Transcriptomic and lipidomic profiling of eicosanoid/docosanoid signalling in affected and non-affected skin of human atopic dermatitis patients. / Törőcsik, D.; Weise, Christin; Gericke, Janine; Szegedi, A.; Lucas, Renata; Mihaly, Johanna; Worm, Margitta; Rühl, Ralph.

In: Experimental Dermatology, Vol. 28, No. 2, 01.02.2019, p. 177-189.

Research output: Article

Törőcsik, D. ; Weise, Christin ; Gericke, Janine ; Szegedi, A. ; Lucas, Renata ; Mihaly, Johanna ; Worm, Margitta ; Rühl, Ralph. / Transcriptomic and lipidomic profiling of eicosanoid/docosanoid signalling in affected and non-affected skin of human atopic dermatitis patients. In: Experimental Dermatology. 2019 ; Vol. 28, No. 2. pp. 177-189.
@article{148ddbf6e7064ce5a5a90222399d2224,
title = "Transcriptomic and lipidomic profiling of eicosanoid/docosanoid signalling in affected and non-affected skin of human atopic dermatitis patients",
abstract = "Lipoxygenases (LOX) and cyclooxygenase (COX) are the main enzymes for PUFA metabolism to highly bio-active prostaglandins, leukotrienes, thromboxanes, lipoxins, resolvins and protectins. LOX and COX pathways are important for the regulation of pro-inflammatory or pro-resolving metabolite synthesis and metabolism for various inflammatory diseases such as atopic dermatitis (AD). In this study, we determined PUFAs and PUFA metabolites in serum as well as affected and non-affected skin samples from AD patients and the dermal expression of various enzymes, binding proteins and receptors involved in these LOX and COX pathways. Decreased EPA and DHA levels in serum and reduced EPA level in affected and non-affected skin were found; in addition, n3/n6-PUFA ratios were lower in affected and non-affected skin and serum. Mono-hydroxylated PUFA metabolites of AA, EPA, DHA and the sum of AA, EPA and DHA metabolites were increased in affected and non-affected skin. COX1 and ALOX12B expression, COX and 12/15-LOX metabolites as well as various lipids, which are known to induce itch (12-HETE, LTB4, TXB2, PGE2 and PGF2) and the ratio of pro-inflammatory vs pro-resolving lipid mediators in non-affected and affected skin as well as in the serum of AD patients were increased, while n3/n6-PUFAs and metabolite ratios were lower in non-affected and affected AD skin. Expression of COX1 and COX-metabolites was even higher in non-affected AD skin. To conclude, 12/15-LOX and COX pathways were mainly upregulated, while n3/n6-PUFA and metabolite ratios were lower in AD patients skin. All these parameters are a hallmark of a pro-inflammatory and non-resolving environment in affected and partly in non-affected skin of AD patients.",
keywords = "leukotriens, lipid mediators, lipids, PPAR-mediated signalling, prostaglandins, skin inflammation",
author = "D. T{\"o}rőcsik and Christin Weise and Janine Gericke and A. Szegedi and Renata Lucas and Johanna Mihaly and Margitta Worm and Ralph R{\"u}hl",
year = "2019",
month = "2",
day = "1",
doi = "10.1111/exd.13867",
language = "English",
volume = "28",
pages = "177--189",
journal = "Experimental Dermatology",
issn = "0906-6705",
publisher = "Wiley-Blackwell",
number = "2",

}

TY - JOUR

T1 - Transcriptomic and lipidomic profiling of eicosanoid/docosanoid signalling in affected and non-affected skin of human atopic dermatitis patients

AU - Törőcsik, D.

AU - Weise, Christin

AU - Gericke, Janine

AU - Szegedi, A.

AU - Lucas, Renata

AU - Mihaly, Johanna

AU - Worm, Margitta

AU - Rühl, Ralph

PY - 2019/2/1

Y1 - 2019/2/1

N2 - Lipoxygenases (LOX) and cyclooxygenase (COX) are the main enzymes for PUFA metabolism to highly bio-active prostaglandins, leukotrienes, thromboxanes, lipoxins, resolvins and protectins. LOX and COX pathways are important for the regulation of pro-inflammatory or pro-resolving metabolite synthesis and metabolism for various inflammatory diseases such as atopic dermatitis (AD). In this study, we determined PUFAs and PUFA metabolites in serum as well as affected and non-affected skin samples from AD patients and the dermal expression of various enzymes, binding proteins and receptors involved in these LOX and COX pathways. Decreased EPA and DHA levels in serum and reduced EPA level in affected and non-affected skin were found; in addition, n3/n6-PUFA ratios were lower in affected and non-affected skin and serum. Mono-hydroxylated PUFA metabolites of AA, EPA, DHA and the sum of AA, EPA and DHA metabolites were increased in affected and non-affected skin. COX1 and ALOX12B expression, COX and 12/15-LOX metabolites as well as various lipids, which are known to induce itch (12-HETE, LTB4, TXB2, PGE2 and PGF2) and the ratio of pro-inflammatory vs pro-resolving lipid mediators in non-affected and affected skin as well as in the serum of AD patients were increased, while n3/n6-PUFAs and metabolite ratios were lower in non-affected and affected AD skin. Expression of COX1 and COX-metabolites was even higher in non-affected AD skin. To conclude, 12/15-LOX and COX pathways were mainly upregulated, while n3/n6-PUFA and metabolite ratios were lower in AD patients skin. All these parameters are a hallmark of a pro-inflammatory and non-resolving environment in affected and partly in non-affected skin of AD patients.

AB - Lipoxygenases (LOX) and cyclooxygenase (COX) are the main enzymes for PUFA metabolism to highly bio-active prostaglandins, leukotrienes, thromboxanes, lipoxins, resolvins and protectins. LOX and COX pathways are important for the regulation of pro-inflammatory or pro-resolving metabolite synthesis and metabolism for various inflammatory diseases such as atopic dermatitis (AD). In this study, we determined PUFAs and PUFA metabolites in serum as well as affected and non-affected skin samples from AD patients and the dermal expression of various enzymes, binding proteins and receptors involved in these LOX and COX pathways. Decreased EPA and DHA levels in serum and reduced EPA level in affected and non-affected skin were found; in addition, n3/n6-PUFA ratios were lower in affected and non-affected skin and serum. Mono-hydroxylated PUFA metabolites of AA, EPA, DHA and the sum of AA, EPA and DHA metabolites were increased in affected and non-affected skin. COX1 and ALOX12B expression, COX and 12/15-LOX metabolites as well as various lipids, which are known to induce itch (12-HETE, LTB4, TXB2, PGE2 and PGF2) and the ratio of pro-inflammatory vs pro-resolving lipid mediators in non-affected and affected skin as well as in the serum of AD patients were increased, while n3/n6-PUFAs and metabolite ratios were lower in non-affected and affected AD skin. Expression of COX1 and COX-metabolites was even higher in non-affected AD skin. To conclude, 12/15-LOX and COX pathways were mainly upregulated, while n3/n6-PUFA and metabolite ratios were lower in AD patients skin. All these parameters are a hallmark of a pro-inflammatory and non-resolving environment in affected and partly in non-affected skin of AD patients.

KW - leukotriens

KW - lipid mediators

KW - lipids

KW - PPAR-mediated signalling

KW - prostaglandins

KW - skin inflammation

UR - http://www.scopus.com/inward/record.url?scp=85060776962&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85060776962&partnerID=8YFLogxK

U2 - 10.1111/exd.13867

DO - 10.1111/exd.13867

M3 - Article

VL - 28

SP - 177

EP - 189

JO - Experimental Dermatology

JF - Experimental Dermatology

SN - 0906-6705

IS - 2

ER -