ARTICLE | doi:10.20944/preprints201809.0222.v1
Subject: Medicine And Pharmacology, Pathology And Pathobiology Keywords: psoriasis, arthritis, inflammation, granulocytes, redox signaling, oxidative stress, lipid peroxidation, 4-hydroxynonenal, lipids, endocannabinoid system
Online: 12 September 2018 (13:43:16 CEST)
Inflammatory granulocytes are characterized by oxidative burst, which may promote oxidative stress and lipid modification both in affected tissues and on systemic level. On the other hand, redox signaling involving lipid peroxidation products acting as second messengers of free radicals play important, not yet fully understood, roles in pathophysiology of inflammation and various stress-associated disorders. Therefore, the aim of this study was to evaluate the onset of oxidative stress and alterations of enzyme-dependent lipid metabolism resulting from redox imbalance in granulocytes and plasma obtained from patients with psoriasis vulgaris or psoriatic arthritis, in comparison to the healthy subjects. The results obtained revealed enhanced activity of pro-oxidant enzymes NADPH and xanthine oxidases in granulocytes, with a decrease of enzymatic and non-enzymatic antioxidants in plasma of psoriatic patients. The Nrf2 and its regulators were increased in both forms of psoriasis, while HO-1 levels were increased only in psoriasis vulgaris. Redox imbalance was associated with decreased levels of phospholipids and of free PUFAs, but with enhanced activity of enzymes involved in lipid metabolism (PLA2, PAF-AH COX1/2) and increased lipid peroxidation products 4-hydroxynonenal (4-HNE), isoprostanes and neuroprostanes. Increased endocannabinoids and GPR55 were observed in both forms of the disease, while expression of CB1 was increased only in pateints with psoriatic arthritis, opposite to CB2, which was increased only in psoriasis vulgaris. Protein modifications by ROS and lipid peroxidation product 4-HNE promoted apoptosis of granulocytes by increased caspases in both forms of psoriasis. This study indicates that excessive activation of granulocytes, causing oxidative stress and lipid modifications, is an important pathophysiology of psoriasis. Consequently, lower Nrf2 activity and CB2 expression may promote progression of psoriasis into advanced, arthritic form of the disease.
ARTICLE | doi:10.20944/preprints202209.0298.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: granulocytes; COVID-19; antioxidants; inflammation; eicosanoids; receptors-coupled G protein; SOD
Online: 20 September 2022 (09:24:19 CEST)
Abstract: It is assumed that upon SARS-CoV-2 infection granulocytes can undergo potentially destructive oxidative burst. Therefore, the aim of this study was to evaluate some parameters of redox and inflammatory signaling in granulocytes of recovered and of deceased COVID-19 pa-tients. Granulocytes were isolated from the blood of 32 COVID-19 patients on admission to the hospital (16 survived and 16 died within a week). The levels of proteins (immunoassay), eico-sanoids (UPLC-MS) and antioxidants activity (spectrophotometry) were examined. Enhanced activation of Nrf2 and NFκB and the levels of heme oxygenase and proinflammatory cytokines where found in granulocytes of all COVID-19 patients, while Cu,Zn-SOD and Mn-SOD activities were decreased, especially in deceased patients. Moreover, in patients who died increased levels of pro-inflammatory eicosanoids (PGE2 and TXB2) and decreased of anti-inflammatory (15d-PGJ2 and 5-HETE) were observed. However TXB2 was decreased, and IL-2 and IL-10 levels were in-creased in survivors, if compared both to healthy subjects and deceased patients, who did not change their cytokine generation. Therefore, it seems that by triggering transcription factors granulocytes activate redox signaling, leading to the production of pro-inflammatory eicosanoids, while reducing cellular antioxidant capacity via SOD, they express altered response to COVID-19, which might result in the onset of the vicious cycle of systemic oxidative stress in deceased patients.