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J Invest Dermatol. 2018 Jul;138(7):1518-1528. doi: 10.1016/j.jid.2018.02.003. Epub 2018 Feb 15.

Bioactive Lipid Mediator Profiles in Human Psoriasis Skin and Blood.

Author information

1
Section of Inflammation and Cardiometabolic Diseases, Cardio-Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
2
Lipid Mediators, Inflammation, and Pain Unit, Laboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
3
Bristol-Myers Squibb Clinical Development, Princeton, New Jersey, USA.
4
Lipid Mediators, Inflammation, and Pain Unit, Laboratory of Clinical Investigation, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA; Intramural Program of the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, Maryland, USA; FOODplus Research Centre, School of Agriculture Food and Wine, The University of Adelaide, Adelaide, Australia.
5
Section of Inflammation and Cardiometabolic Diseases, Cardio-Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA. Electronic address: nehal.mehta@nih.gov.

Abstract

Psoriasis is a chronic immune-mediated disease that represents a unique model for investigating inflammation at local and systemic levels. Bioactive lipid mediators (LMs) are potent compounds reported to play a role in the development and resolution of inflammation. Currently, it is not known to what extent these LMs are involved in psoriasis pathophysiology and related metabolic dysfunction. Here, we use targeted and untargeted liquid chromatography-tandem mass spectrometry approaches to quantify LMs in skin and peripheral blood from psoriasis patients and compared them with those of healthy individuals. Lesional psoriasis skin was abundant in arachidonic acid metabolites, as 8-, 12- and 15-hydroxyeicosatetraenoic acid, compared with adjacent nonlesional and skin from healthy individuals. Additionally, a linoleic acid-derived LM, 13-hydroxyoctadecadienoic acid, was significantly increased compared with healthy skin (607.9 ng/g vs. 5.4 ng/g, P = 0.001). These psoriasis skin differences were accompanied by plasma decreases in antioxidant markers, including glutathione, and impaired lipolysis characterized by lower concentrations of primary and secondary bile acids. In conclusion, our study shows that psoriasis skin and blood have disease-specific phenotype profiles of bioactive LMs represented by omega-6 fatty acid-oxidized derivatives. These findings provide insights into psoriasis pathophysiology that could potentially contribute to new biomarkers and therapeutics.

PMID:
29454560
PMCID:
PMC6121727
DOI:
10.1016/j.jid.2018.02.003
[Indexed for MEDLINE]
Free PMC Article

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