Unbalanced Sphingolipid Metabolism and Its Implications for the Pathogenesis of Psoriasis

Abstract

Sphingolipids (SLs), which have structural and biological responsibilities in the human epidermis, are importantly involved in the maintenance of the skin barrier and regulate cellular processes, such as the proliferation, differentiation and apoptosis of keratinocytes (KCs). As many dermatologic diseases, including psoriasis (PsO), intricately characterized by perturbations in these cellular processes, are associated with altered composition and unbalanced metabolism of epidermal SLs, more education to precisely determine the role of SLs, especially in the pathogenesis of skin disorders, is needed. PsO is caused by a complex interplay between skin barrier disruption, immune dysregulation, host genetics and environmental triggers. The contribution of particular cellular compartments and organelles in SL metabolism, a process related to dysfunction of lysosomes in PsO, seems to have a significant impact on lysosomal signalling linked to a modulation of the immune-mediated inflammation accompanying this dermatosis and is not fully understood. It is also worth noting that a prominent skin disorder, such as PsO, has diminished levels of the main epidermal SL ceramide (Cer), reflecting altered SL metabolism, that may contribute not only to pathogenesis but also to disease severity and/or progression. This review provides a brief synopsis of the implications of SLs in PsO, aims to elucidate the roles of these molecules in complex cellular processes deregulated in diseased skin tissue and highlights the need for increased research in the field. The significance of SLs as structural and signalling molecules and their actions in inflammation, in which these components are factors responsible for vascular endothelium abnormalities in the development of PsO, are discussed.

Sphingolipids and Kidney Disease: Possible Role of Preeclampsia and Intrauterine Growth Restriction (IUGR)

“…In the presence of stress stimuli, sphingomyelin is broken down to ceramide and phosphocholine. This reaction is mediated by sphingomyelinase 29,30 . Undesired complex sphingolipids such as glycosphingolipids may be broken down in the acidic environment of lysosomes or late endosomes to ceramide 29 .…”

“…This reaction is mediated by sphingomyelinase 29,30 . Undesired complex sphingolipids such as glycosphingolipids may be broken down in the acidic environment of lysosomes or late endosomes to ceramide 29 . Complex glycosphingolipids are degraded through sequential hydrolysis of terminal hydrophilic moieties by hydrolases, where glucose or galactose is removed by β-glucosidases or galactosidase, respectively, to produce ceramide.…”

Therapeutic implications and role of serum sphingolipids on psoriasis severity after narrow band ultraviolet B treatment: A cross sectional controlled study

“…Moreover, it plays an important signaling role in epidermal barrier function and migration of endothelial cells protecting and maintaining vascular integrity. 10 Notably, up-regulation of S1P phosphatase 2 (SPP2) mRNA expression was identified in psoriatic lesions biopsy samples. 11 The impact of obesity on the circulating levels of sphigolipids was studied in a case control study and S1P higher concentrations were found in all psoriatic patients compared to healthy controls.…”

Research progress and perspective in metabolism and metabolomics of psoriasis

“…In addition, LPC is involved in inducing apoptosis and promoting reactive oxygen species production to enhance oxidative stress. [ 58 , 106 ]…”

“…First, it induces DC apoptosis by downregulating survival signaling pathways, such as NF-κB and protein kinase B (PKB). [ 106 ] In addition, ceramides may participate in the induction of DC maturation and promote the production of major histocompatibility complex class I molecules and the secretion of proinflammatory cytokines, such as IL-12 and TNF-α. [ 107 ] Moreover, S1P has anti-inflammatory effects by reducing the production of IL-12 and IL-23 by the shared p40 subunit in DCs, thereby inhibiting DC crosstalk with activated keratinogenic cells.…”