sphingosine-1-phosphate and Acne-Vulgaris

Sphingolipids have long been viewed as rather passive structural components of cellular membranes. More recently, it has become evident that metabolism of sphingomyelin yields several lipid mediators that evoke diverse and specific responses in different cell types. One sphingomyelin derivate, sphingosine-1-phosphate (S1P), has attracted particular attention for its effect on epidermal cells, which differs from those on most other cell types. S1P inhibits keratinocyte proliferation and induces keratinocyte differentiation and migration, suggesting a role for S1P in the re-epithelialization of wounds. The migratory response involves the phosphorylation and activation of Smad3. In epithelial tumors, S1P signaling has been linked with potential oncogenic effects, but has also been found to inhibit metastasis in a mouse melanoma model. S1P promotes endothelial cell survival, acts as a chemoattractant for vascular cells, and exerts a protective effect on the endothelial barrier. Conversely, S1P receptor knockout leads to embryonic lethality mainly due to impaired vascular maturation. S1P presumably modulates peripheral T-lymphocyte levels by stimulating their egress from lymphoid organs rather than by promoting T-cell proliferation. The S1P analog FTY720 (fingolimod) acts as a functional antagonist by inhibiting lymphocyte egress, and thus holds great promise as an immunosuppressant drug for the prevention of allograft rejection and treatment of T-lymphocyte-driven inflammatory skin diseases, such as lupus erythematosus, psoriasis, and atopic dermatitis. Topical use of S1P and other sphingosine compounds is also under investigation, particularly for the treatment of acne vulgaris.

Topics: Acne Vulgaris; Animals; Cell Transformation, Neoplastic; Connective Tissue; Epidermis; Fingolimod Hydrochloride; Humans; Immunity; Immunosuppressive Agents; Lysophospholipids; Propylene Glycols; Receptors, Lysosphingolipid; Signal Transduction; Skin; Sphingosine; T-Lymphocytes

Limited data are available on serum levels of different sphingomyelin (SM) and ceramide (CER) species in acne vulgaris (AV).. This study aimed to identify circulating levels of neutral sphingomyelinase activity (N-SMase), ceramide-1-phosphate (C1P), sphingosine-1-phosphate (S1P), C16-C24 SMs and C16-C24 CERs in AV patients and controls.. Serum was collected from 30 AV patients and 20 age, gender-matched control subjects. Serum levels of C16-C24 SMs and C16-C24 CERs were determined by an optimized multiple reaction monitoring (MRM) method using ultra fast-liquid chromatography (UFLC) coupled with tandem mass spectrometry (MS/MS). Serum activity of N-SMase was assayed by standard kit methods, C1P and S1P levels were determined by enzyme-linked immunosorbent assay (ELISA).. A significant increase was observed in serum levels of C16 SM in patients with AV compared to controls. No significant difference was found in C18 and C24 SM levels between the two groups. Very-long-chain C24 CER was significantly decreased in AV patients compared to controls. Long chain C16-C20 CER levels showed no significant difference between AV patients and controls. A significant positive correlation was found between serum total cholesterol levels and all measured SMs and CERs in both the control and patient groups. Patients with AV had increased circulating levels of C16 SM, C1P and lower circulating levels of C24 CER compared to healthy controls, which may provide prognostic value for the disease.. Future studies are needed to understand the role of altered sphingolipid levels in the pathophysiology of AV.

Topics: Acne Vulgaris; Adult; Ceramides; Cholesterol; Female; Humans; Lysophospholipids; Metabolomics; Sphingolipids; Sphingomyelin Phosphodiesterase; Sphingomyelins; Sphingosine