Expression signature of epidermolysis bullosa simplex
The extent of epidermal fatty acid oxygenase activation in non-psoriatic dermatoses and the nature of these oxygenases are not known. The monohydroxylated fatty acid derivatives produced in vivo and trapped in skin scales or produced in vitro by oxygenases preserved in scales were analyzed by high performance liquid chromatography in 10 patients with non-psoriatic dermatoses. Evidence for 15-lipoxygenase activation included the finding of 15(S)-hydroxyeicosatetraenoic acid (HETE) in scales from seven patients and the production of 15(S)-[14C]HETE and 13(S)-[14C]hydroxyoctadecadienoic acid (HODE) during scale incubations, respectively, with [14C]arachidonic and [14C]linoleic acid. Evidence for the activation of an arachidonic acid 12(R)-oxygenase included the finding of 12(R)-HETE in scales from eight patients and the production of 12(R)-[14C]HETE during scale incubations with [14C]arachidonic acid. 13-HODE was the predominant fatty acid derivative present in scale extracts; its lack of enantiopurity (mean S/R = 3.1) and the substantial formation of 9-HODE (mean S/R = 0.6; 9/13-HODE = 0.43) suggest its derivation from 15-lipoxygenase and a second oxygenase. The levels of 15(S)-HETE and 12(R)-HETE had a 125- to 144-fold range and were highest in scales from a patient with erythroderma and in three psoriatic scale samples similarly analyzed. These findings indicate that 15-lipoxygenase, most likely of keratinocyte origin, and an arachidonic acid 12(R)oxygenase of unknown type and cell origin are activated in diverse dermatoses.