Altered Lipid Metabolism in Blood Mononuclear Cells of Psoriatic Patients Indicates Differential Changes in Psoriasis Vulgaris and Psoriatic Arthritis

Abstract

The aim of this study was to investigate possible stress-associated disturbances in lipid metabolism in mononuclear cells, mainly lymphocytes of patients with psoriasis vulgaris (Ps, n = 32) or with psoriatic arthritis (PsA, n = 16) in respect to the healthy volunteers (n = 16). The results showed disturbances in lipid metabolism of psoriatic patients reflected by different phospholipid profiles. The levels of non-enzymatic lipid metabolites associated with oxidative stress 8-isoprostaglandin F2α (8-isoPGF2α) and free 4-hydroxynonenal (4-HNE) were higher in PsA, although levels of 4-HNE-His adducts were higher in Ps. In the case of the enzymatic metabolism of lipids, enhanced levels of endocannabinoids were observed in both forms of psoriasis, while higher expression of their receptors and activities of phospholipases were detected only in Ps. Moreover, cyclooxygenase-1 (COX-1) activity was enhanced only in Ps, but cyclooxygenase-2 (COX-2) was enhanced both in Ps and PsA, generating higher levels of eicosanoids: prostaglandin E1 (PGE1), leukotriene B4 (LTB4), 13-hydroxyoctadecadienoic acid (13HODE), thromboxane B2 (TXB2). Surprisingly, some of major eicosanoids 15-d-PGJ2 (15-deoxy-Δ12,14-prostaglandin J2), 15-hydroxyeicosatetraenoic acid (15-HETE) were elevated in Ps and reduced in PsA. The results of our study revealed changes in lipid metabolism with enhancement of immune system-modulating mediators in psoriatic mononuclear cells. Evaluating further differential stress responses in Ps and PsA affecting lipid metabolism and immunity might be useful to improve the prevention and therapeutic treatments of psoriasis.

Reduced Proteasome Activity and Enhanced Autophagy in Blood Cells of Psoriatic Patients

“…Phospholipids, especially their polyunsaturated fatty acids, are extremely susceptible to ROS, and as a result of oxidative fragmentation of hydrocarbon chains of these acids, reactive aldehydes are formed, including 4-HNE [ 39 ]. Elevated levels of 4-HNE were observed in the blood cells (erythrocytes, granulocytes, and lymphocytes) of patients with psoriasis, which confirms previous results showing the same effect in granulocytes and lymphocytes as well as plasma of patients [ 11 , 12 ].…”

“…Psoriasis is an inflammatory immune disease with a pathogenesis that is incompletely understood. However, it is clear that the development of this disease is accompanied by oxidative stress resulting from increased ROS production and disruption of antioxidant protection both local in skin cells and systemic in blood cells, as we have shown in previous studies [ 11 , 12 ]. Such conditions favor the oxidative modifications of the cellular components, including proteins, lipids, and DNA, and many studies have shown elevated levels of oxidative stress markers in serum/plasma and blood cells (erythrocytes, lymphocytes, and granulocytes) in patients with psoriasis [ 8 , 9 , 10 , 37 ].…”

“…Recent reports have confirmed that psoriasis is accompanied by enhanced lipid peroxidation, demonstrated by the increased generation of α,β unsaturated reactive aldehydes (e.g., 4-HNE) that form adducts with proteins. These products may play an important role in the pathophysiology of psoriasis [ 11 , 12 , 16 ].…”

Cannabidiol Effects on Phospholipid Metabolism in Keratinocytes from Patients with Psoriasis Vulgaris

“…Although endogenous antioxidants counteract the effects of ROS overproduction, the excessively high and/or long-lasting presence of ROS in cells, such as in disease conditions, leads to oxidative stress. Recently, we have shown a shift in redox balance towards oxidative conditions with the formation of oxidative stress in plasma, lymphocytes, and granulocytes of patients with psoriasis, leading to the intensification of oxidative modifications of lipids, proteins, and other endogenous compounds [49][50][51]. Different populations of activated leukocytes infiltrating skin lesions also lead to an increase in the level of local oxidants and cause a pro-inflammatory response, as well as oxidative modifications of proteins and lipids in skin cells, especially in keratinocytes [52,53].…”

Interleukin-17A and Keratinocytes in Psoriasis

“…Psoriasis is also significantly comorbid with other autoimmune diseases, such as bullous pemphigoid [20][21][22][23][24]. Psoriasis is frequently associated with cardiovascular diseases, metabolic diseases, and renal disorders [25][26][27][28][29][30][31][32][33][34][35][36]. Cancer risk is slightly higher in patients with psoriasis [37].…”