Alexander V Sorokin1, Paul C Norris2, Justin T English2, Amit K Dey1, Abhishek Chaturvedi1, Yvonne Baumer1, Joanna Silverman1, Martin P Playford1, Charles N Serhan2, Nehal N Mehta3. 1. Section of Inflammation and Cardiometabolic Diseases, Cardio-Pulmonary Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA. 2. Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative, and Pain Medicine, Harvard Institutes of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. 3. Section of Inflammation and Cardiometabolic Diseases, Cardio-Pulmonary Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address: nehal.mehta@nih.gov.
Abstract
BACKGROUND: Psoriasis (PSO) is an immune-mediated inflammatory disease associated with metabolic and cardiovascular comorbidities. It is now known that resolution of inflammation is an active process locally controlled by specialized proresolving mediators (SPMs), named resolvins (Rvs), protectins, and maresins. OBJECTIVE: It is unknown whether these potent lipid mediators (LMs) are involved in PSO pathophysiology and if the skin and blood have disease-specific SPMs phenotype profiles. METHODS: We used liquid chromatography-tandem mass spectrometry-based LM metabololipidomics to obtain skin and peripheral blood LM profiles from PSO compared to healthy subjects. Some LMs were tested in cell culture experiments with corresponding gene expression and protein concentration analyses. RESULTS: The levels of several LM were significantly elevated in lesional PSO skin compared to nonlesional and skin from healthy subjects. Particularly, RvD5, protectins Dx, and aspirin-triggered forms of lipoxin were present only in lesional PSO skin, whereas protectin D1 was present in nonlesional PSO skin. To determine specific roles of SPMs on skin-related inflammatory cytokines, RvD1 and RvD5 were incubated with human keratinocytes. RvD1 and RvD5 reduced the expression levels of interleukin 24 and S100A12, whereas only RvD1 significantly abrogated interleukin-24 production by keratinocytes. CONCLUSIONS: These findings suggest that an imbalance between locally produced proresolution and proinflammatory LMs identified in PSO skin and blood compartments might play a role in PSO pathophysiology. Moreover, some of the PSO-related cytokines can be modified by specific SPMs and involved mechanisms support investigation of targeting novel proresolving lipid mediators as a therapy for PSO. Published by Elsevier Inc.
BACKGROUND:Psoriasis (PSO) is an immune-mediated inflammatory disease associated with metabolic and cardiovascular comorbidities. It is now known that resolution of inflammation is an active process locally controlled by specialized proresolving mediators (SPMs), named resolvins (Rvs), protectins, and maresins. OBJECTIVE: It is unknown whether these potent lipid mediators (LMs) are involved in PSO pathophysiology and if the skin and blood have disease-specific SPMs phenotype profiles. METHODS: We used liquid chromatography-tandem mass spectrometry-based LM metabololipidomics to obtain skin and peripheral blood LM profiles from PSO compared to healthy subjects. Some LMs were tested in cell culture experiments with corresponding gene expression and protein concentration analyses. RESULTS: The levels of several LM were significantly elevated in lesional PSO skin compared to nonlesional and skin from healthy subjects. Particularly, RvD5, protectins Dx, and aspirin-triggered forms of lipoxin were present only in lesional PSO skin, whereas protectin D1 was present in nonlesional PSO skin. To determine specific roles of SPMs on skin-related inflammatory cytokines, RvD1 and RvD5 were incubated with human keratinocytes. RvD1 and RvD5 reduced the expression levels of interleukin 24 and S100A12, whereas only RvD1 significantly abrogated interleukin-24 production by keratinocytes. CONCLUSIONS: These findings suggest that an imbalance between locally produced proresolution and proinflammatory LMs identified in PSO skin and blood compartments might play a role in PSO pathophysiology. Moreover, some of the PSO-related cytokines can be modified by specific SPMs and involved mechanisms support investigation of targeting novel proresolving lipid mediators as a therapy for PSO. Published by Elsevier Inc.
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