Extracellular superoxide dismutase ameliorates house dust mite-induced atopic dermatitis-like skin inflammation and inhibits mast cell activation in mice.

Extracellular superoxide dismutase (EC-SOD) is an enzyme that catalyses the dismutation of superoxide anions. It has multiple functions, such as reactive oxygen species scavenging, anti-angiogenic, anti-inflammatory, antichemotatic and antitumor activities. Recently, we demonstrated that EC-SOD inhibits ovalbumin-induced allergic airway inflammation in mice. However, the anti-allergic effect of EC-SOD on skin tissue and the role of EC-SOD in mast cells, which are important for allergic responses, have not been well studied. In this study, we investigated whether EC-SOD can alleviate atopic dermatitis in mice and inhibit mast cell activation. Treatment with human recombinant EC-SOD ameliorated house dust mite-induced atopic dermatitis in mice. Furthermore, the levels of pro-allergic cytokine gene expression and histamine release increased in EC-SOD KO mast cells and decreased in EC-SOD overexpressing mast cells, suggesting that EC-SOD inhibits mast cell activation. Consistently, a passive cutaneous anaphylaxis experiment showed more blood leakage from EC-SOD KO mouse ear skin, implying that the lack of EC-SOD increases allergic responses. These results suggest that EC-SOD inhibits mast cell activation and atopic dermatitis and that the loss of EC-SOD causes more severe allergic responses, implying that EC-SOD might be a good drug candidate for treatment of allergic disorders, such as atopic dermatitis.