The Interplay between Bioactive Sphingolipids in the Psoriatic Skin and the Severity of the Disease

Abstract

Psoriasis is a complex chronic immunologically mediated disease that may involve skin, nails, and joints. It is characterized by hyperproliferation, deregulated differentiation, and impaired apoptosis of keratinocytes. Sphingolipids, namely ceramide, sphingosine-1-phosphate, sphingosine, sphingomyelin, and sphinganine-1-phosphate, are signal molecules that may regulate cell growth, immune reactions, and apoptosis. Fifteen patients with psoriasis and seventeen healthy persons were enrolled in the study. Skin samples were taken from psoriatic lesions and non-lesional areas. Tissue concentration of ceramides, sphingosine-1-phosphate, sphingosine, sphingomyelin, and sphinganine-1-phosphate was measured by liquid chromatography. We assessed that all levels of ceramides, sphingosine-1-phosphate, sphingosine, sphingomyelin, and sphinganine-1-phosphate were higher in lesioned psoriatic skin than in non-affected skin. The profile of bioactive lipids in the lesional skin of patients with psoriasis differed significantly from non-involved psoriatic skin and skin in healthy subjects.

Keywords: ceramide; psoriasis; sphinganine; sphinganine-1-phosphate; sphingosine; sphingosine-1-phosphate.

Figure 1

Comparison between sphingolipids in healthy (CTRL), psoriatic lesional (PSO (l)), and psoriatic non-lesional (PSO (nl)) skin. (A) Amount of sphinganine (SFA) (pmol/mg of tissue). (B) Amount of sphinganine-1-phosphate (SFA1P) (pmol/mg of tissue). (C) Amount of sphingosine-1-phosphate (S1P) (pmol/mg of tissue). (D) Amount of sphingosine (SFO) (pmol/mg of tissue). (E) Amount of ceramide (CER) (pmol/mg of tissue). (F) The ratio of sphinganine and sphingosine. Significance markers: a signifies different vs. CTRL (p < 0.05) and b signifies different vs. PSO (NL) (p < 0.05).

Figure 2

Correlation matrix (heatmap). Pearson correlation coefficients are depicted as shades of blue (positive correlation) or red (negative correlation). (A) Correlation matrix for psoriatic non-lesional (PSO (nl)) skin. (B) Correlation matrix for psoriatic lesional (PSO (l)) skin. CER—ceramide; Desq.—desquamation; Eryth.—erythema; Ind.—induration; PASI_l—psoriasis area severity index_lesional; PASI_t—psoriasis area severity index_total; S1P—sphingosine-1-phosphate; SFA—sphinganine; SFA1P—sphinganine-1-phosphate; SFO—sphingosine.