Arginase is overactive in psoriatic skin

Area of Science:

• Dermatology
• Biochemistry
• Wound Healing

Background:

• Psoriatic keratinocytes exhibit poor differentiation and hyperproliferation.
• Nitric oxide (NO) plays a dual role: low concentrations promote proliferation, while high concentrations induce differentiation.
• Inducible NO synthase (iNOS) and arginase are overexpressed in psoriatic skin, with arginase potentially limiting NO production by consuming its substrate, arginine.

Purpose of the Study:

• To investigate elevated arginase activity in psoriatic skin.
• To assess the therapeutic potential of exogenous NO in improving psoriatic plaques.

Main Methods:

• Quantified L-arginine, L-citrulline, and L-ornithine concentrations in psoriatic and healthy skin using high-performance liquid chromatography.
• Administered a nitric oxide (NO) donor and vehicle control to symmetrical psoriatic plaques in four patients.
• Evaluated plaque severity (size, erythema, induration, scaling) before and after 6 weeks of treatment.

Main Results:

• Nonlesional psoriatic skin showed significantly higher concentrations of ornithine (arginase product) and lower concentrations of arginine (substrate) compared to healthy skin.
• Topical NO donor treatment led to a significant clinical improvement in psoriatic plaques, reducing severity scores from a baseline of 100% to 35% +/- 16%.

Conclusions:

• Arginase hyperactivity in psoriatic skin contributes to increased arginine consumption.
• This suggests a relative deficiency in NO synthase-derived NO production in psoriatic lesions.
• Nitric oxide donors represent a promising topical therapeutic strategy for psoriasis management.