Arginase is overactive in psoriatic skin

Abstract

Background Psoriatic keratinocytes are poorly differentiated and hyperproliferative. Low concentrations of nitric oxide (NO) induce keratinocyte proliferation, while high concentrations induce differentiation. The NO‐producing enzyme inducible NO synthase is overexpressed in psoriatic skin, but so is arginase. The overexpressed arginase competes for arginine, the common substrate for both enzymes, and may reduce NO production. Objectives To determine whether arginase activity is elevated in psoriatic skin and whether exogenous NO will improve psoriatic plaques. Methods Tape strips were taken from healthy skin of eight control subjects and nonlesional skin of eight patients with psoriasis and l‐arginine, l‐citrulline and l‐ornithine concentrations measured by high‐performance liquid chromatography. In a second study, four psoriatic patients with a pair of similar symmetrical plaques were treated with an NO donor and vehicle control. Plaques were scored for size, erythema, induration and scaling at the start and after 6 weeks of treatment. Results Ornithine, the end‐product of arginase, was at higher concentrations in nonlesional psoriatic than in healthy skin (mean ± SEM 2·08 ± 0·98 vs. 1·13 ± 0·44 μg mg⁻¹ protein; P = 0·0002). Arginine, its substrate, was at lower concentrations. Topical application of an NO donor improved psoriatic plaques clinically [mean ± SD reduction in severity from baseline score (100%) to 35% ± 16% in active NO donor and to 93% ± 10% in control]. Conclusions Arginase is overactive in psoriatic skin, leading to a relative increase in the consumption of arginine. We therefore hypothesize a relative decrease in NO synthase‐derived NO production. NO donors may be effective topical treatments for psoriasis.