Deficiency of inducible nitric oxide synthase (iNOS) enhances MC903-induced atopic dermatitis-like inflammation in mice.

The production and secretion of inflammatory mediators contribute to the development of atopic dermatitis (AD). The production of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) is essential for inflammation. Because of the association of iNOS with type 2 inflammation, upregulated iNOS expression in patients with AD suggests a potential pathogenic role of iNOS in AD. In addition, NO regulates keratinocyte and immune cell functions in various inflammatory dermatoses, contributing to the triggering and amplification of inflammation. To ascertain the role of iNOS in inflammation, we utilized a calcipotriol (CPT, MC903)-induced AD-like inflammation in C57BL/6J wildtype mice and iNOS knockout (iNOS KO) mice to investigate the role of iNOS in inflammation. The results showed that iNOS deficiency aggravated dermatitis in MC903-induced inflammation. The expression levels of pro-inflammatory cytokines and chemokines were dramatically elevated, accompanied by the activation of several pro-inflammatory signaling pathways. Moreover, immunofluorescence staining showed that iNOS was mainly expressed in the epidermis and iNOS deficiency significantly promoted the expression of inflammatory factors in keratinocytes. Additionally, topical application of NO donors ameliorated dermatitis symptoms in the iNOS KO mice. These results indicated that epidermal iNOS is important for the occurrence and development of AD. Our results also underscore the therapeutic potential of NO donors in the treatment of AD.