Abstract
Inflammatory granulocytes are characterized by an oxidative burst, which may promote oxidative stress and lipid modification both in affected tissues and on a systemic level. On the other hand, redox signaling involving lipid peroxidation products acting as second messengers of free radicals play important yet not fully understood roles in the 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 nicotinamide adenine dinucleotide phosphate (NADPH) and xanthine oxidases in granulocytes with a decrease of enzymatic and non-enzymatic antioxidants in the plasma of psoriatic patients. The nuclear factor erythroid 2–related factor 2 (Nrf2) and its regulators were increased in both forms of psoriasis while heme oxygenase 1 levels were increased only in psoriasis vulgaris. The redox imbalance was associated with decreased levels of phospholipids and of free polyunsaturated fatty acids but with enhanced activity of enzymes involved in lipid metabolism (phospholipase A2, acetylhydrolase PAF, cyclooxygenases 1 and 2) and increased lipid peroxidation products 4-hydroxynonenal, isoprostanes, and neuroprostanes. Increased endocannabinoids and G protein-coupled receptor 55 were observed in both forms of the disease while expression of the cannabinoid type 1 receptor (CB1) was increased only in patients with psoriatic arthritis, which is opposite to the cannabinoid type 2 receptor. This receptor was increased only in psoriasis vulgaris. Changes in protein expression promoted the apoptosis of granulocytes by increased caspases mainly in psoriasis vulgaris. This study indicates that inhibition of the Nrf2 pathway in psoriatic arthritis promotes a redox imbalance. In addition, increased expression of CB1 receptors leads to increased oxidative stress, lipid modifications, and inflammation, which, in turn, may promote the progression of psoriasis into the advanced, arthritic form of the disease.
Highlights
Under physiological conditions, cells are in a stable state of redox homeostasis, which is maintained by the balance between continuous production of reactive oxygen species (ROS) and antioxidant activities [1]
The onset of psoriasis promoted the formation of oxidative stress both in plasma and in granulocytes of patients with both forms of psoriasis: psoriasis vulgaris (Ps) and psoriatic arthritis (PsA)
An important pathophysiological component of oxidative stress observed in patients with psoriasis vulgaris (Ps) and psoriatic arthritis (PsA) in our study were disturbances in phospholipid psoriasis vulgaris (Ps) and psoriatic arthritis (PsA) in our study were disturbances in phospholipid metabolism
Summary
Cells are in a stable state of redox homeostasis, which is maintained by the balance between continuous production of reactive oxygen species (ROS) and antioxidant activities [1]. Interactions between ROS and antioxidants produce metabolic responses to endogenous and/or exogenous signals/stressors. These signals trigger and modulate the appropriate adaptation processes or activation of the mechanisms causing cellular decay [2]. Cellular redox homeostasis plays a key role in physiology of the cell as well as in numerous pathophysiological processes. Reactive aldehydes, which are products of oxidative fragmentation, may act as second messengers of free radicals and regulatory signaling molecules that modify cellular metabolism and may cause death either through necrosis or apoptosis [7]
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