Bioactive Lipid Mediator Profiles in Human Psoriasis Skin and Blood

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.

Lipidomic profiling of targeted oxylipins with ultra-performance liquid chromatography-tandem mass spectrometry

“…In addition, we used this assay to show that these novel lipids can be altered by changing the amounts of their precursor fatty acids in the diet [70]. It has also been successfully applied for the profiling of these lipid mediators in human psoriasis skin and blood and showed alterations of the targeted mediators by comparing to the healthy individuals [71]. In future studies, we plan to synthesize additional standards of K-E-LAs to expand method performance evaluation, and to incorporate targeted PUFAs in order to investigate how parent PUFA levels relate to their corresponding oxylipin derivatives.…”

cPLA2α Enzyme Inhibition Attenuates Inflammation and Keratinocyte Proliferation

“…Image analysis was performed in the freeware CellProfiler version 3.1.9 [ 48 ]. Firstly, nuclei were segmented from DAPI images using an Ostu 2-class thresholding approach, and were then counted.…”

Transcriptome Profiling Analyses in Psoriasis: A Dynamic Contribution of Keratinocytes to the Pathogenesis

“…PLA2 are potential regulators of epidermal hyperproliferation as they hydrolyze fatty acids in position sn -2 of phospholipids such as linoleic and arachidonic acid, which are then metabolized into bioactive lipid mediators [ 97 ]. Consistent with higher PLA2 gene expression, levels of lipid mediators with pro-inflammatory properties including 12-HETE, LTB 4 and PGE 2 are enhanced in skin lesions [ 98 , 99 ]. These lipids are involved in keratinocyte hyperproliferation and immune cell chemotaxis [ 100 ].…”