The lipoxygenase-hepoxilin pathway is activated in cutaneous plaque lesions of psoriasis

Psoriasis is a common skin disorder that is characterized by hyperkeratosis, epidermal hyperplasia, T-cell and neutrophil recruitment, and changes in the vascular endothelial system. The several upregulated variable lipid mediators, including the eicosanoids, in psoriatic keratinocytes were described previously, although some results were contradictory. Since hepoxilin is less stable than other eicosanoids such as hydroxyeicosatetraenoic acid (HETE), the measurement of hepoxilin is difficult. In this study, to clarify the relationship between hepoxilin/hepoxilin-related fatty acid derivatives and psoriasis vulgaris, we evaluated the amount of production of lipid mediators including hepoxilins in skin tissues of patients with psoriasis vulgaris in comparison with normal controls by high-performance liquid chromatography/mass spectrometry. Most of the hepoxilins and related lipids evaluated in this study tended to be more abundant in the lesional skin from the psoriasis patient group (PPG) than in the skin from controls. Interestingly, 12R-HETE was markedly higher in the skin samples from the PPG. In addition, the lipids produced in the lipoxygenase pathway, including hepoxilin, were elevated in the skin lesions of the PPG compared with those of normal controls, whereas the lipids produced in the cyclooxygenase pathway were decreased in the skin lesions from the PPG. Our results suggest that an imbalance between the lipoxygenase and cyclooxygenase pathways may contribute to psoriatic pathomechanisms.