Cannabidiol-Mediated Changes to the Phospholipid Profile of UVB-Irradiated Keratinocytes from Psoriatic Patients

Abstract

UVB phototherapy is treatment for psoriasis, which increases phospholipid oxidative modifications in the cell membrane of the skin. Therefore, we carried out lipidomic analysis on the keratinocytes of healthy individuals and patients with psoriasis irradiated with UVB and treated with cannabidiol (CBD), phytocannabinoid with antioxidant and anti-inflammatory properties. Our results showed that, in psoriatic keratinocytes phosphatidylcholine (PC), phosphatidylinositol (PI), phosphatidylserine (PS), and ether-linked phosphoethanolamine (PEo), were downregulated, while SM (d41:2) was upregulated. These changes were accompanied by an increase in negative zeta potential, which indicates translocation of PS to the outer layer of the membrane. CBD treatment of psoriatic keratinocytes led to downregulation of PC, PS, and upregulation of certain PEo and an SM species, SM (d42:2), and the zeta potential. However, UVB irradiation of psoriatic keratinocytes resulted in upregulation of PC, PC plasmalogens (PCp), PEo, and a decrease in the negative zeta potential. The exposure of UVB-irradiated cells to CBD led to a decrease in the level of SM (d42:2). Our results suggest that CBD induces pro-apoptotic mechanisms in psoriatic keratinocytes while simultaneously improving the antioxidant properties and preventing the loss of transepidermal water of keratinocytes of patients irradiated with UVB. Thus, CBD has potential therapeutic value in the treatment of psoriasis.

The Differential Effect of Cannabidiol on the Composition and Physicochemical Properties of Keratinocyte and Fibroblast Membranes from Psoriatic Patients and Healthy People

“…The translocation of phospholipids in cell membranes, especially PS, has been recognized as one of the most important markers of the initial phase of apoptosis and is a key signal that triggers phagocytosis in both apoptotic and necrotic cells [58,59]. In addition, the results of our earlier work have shown that CBD treatment of keratinocytes from psoriasis patients causes an increase in SM levels [33]. This finding indicates a correlation between a decrease in PC levels and an increase in SM levels with a reduction in the negative charge of both the epidermis (keratinocytes) and dermis (fibroblasts), which is suggested by the fact that the association constant of negatively charged groups in SM with H + ions has a greater value than the association constant of these groups in PC [60,61].…”

“…The results of this study showed that both UVA and UVB radiation increased the levels of different classes of phospholipids (PC, PE, PS, and PI) in keratinocytes and fibroblasts from both psoriasis patients and healthy individuals. Similarly, literature data demonstrate that fibroblasts exposed to UVA and UVB radiation as well as keratinocytes exposed to UVB radiation have increased PC and PE levels and decreased sphingomyelin (SM) levels [25,33,39,40]. The increase in the PC level and the decrease in the SM level may be related to the activation of sphingomyelinase, which hydrolyzes SM to ceramides and phosphocholine, a compound that mediates the synthesis of PC and may lead to its increase [41].…”

“…It is known that such changes may affect the interactions between cells as well as between cells (especially cell membranes) and ions or molecules in their environment. As a result, they can cause cell function disorders and promote disease development [31][32][33].…”

Effects of Natural Antioxidants on Phospholipid and Ceramide Profiles of 3D-Cultured Skin Fibroblasts Exposed to UVA or UVB Radiation

“…It is well-known that UV radiation, particularly by the induction of oxidative stress, leads to the alteration of skin phospholipid and ceramide metabolism, and consequent changes in their levels and composition [ 42 ]. Until now, most research has focused on the effect of UV radiation on the phospholipid metabolism in major epidermal cells—keratinocytes [ 32 , 43 , 44 ]. Unfortunately, these studies do not reflect the metabolic consequences of UV radiation in the dermis, the deeper layer of the skin, the primary cells of which are the fibroblasts.…”

“…Quantification of the amount of phospholipids in each extract was performed according to the Bartlett and Lewis method [ 31 ]. Experimental procedures of lipid extraction and phospholipid quantification were described in detail in a previously published study based on the same methodology [ 32 ].…”