High-Salt Diet Exacerbates Murine Imiquimod-Induced Psoriasis-like Dermatitis via Activation of Serum- and Glucocorticoid-Inducible Kinase 1

Abstract

Psoriasis is a chronic skin disease manifesting scaly, indurated erythema and an enhanced interleukin (IL)-23/IL-17 immune axis. A high-salt diet (HSD) is known to promote several autoimmune or autoinflammatory diseases. We examined whether an HSD might exacerbate topical imiquimod (IMQ)-induced psoriasis-like dermatitis in mice. Balb/c female mice were fed a normal diet (ND, 0.2% NaCl) or an HSD (4.2% NaCl) for 3 weeks, and 25 mg IMQ was applied to shaved back skin for 5 consecutive days. Compared to ND, the HSD exacerbated IMQ-induced psoriasiform dermatitis with increased scale, skin thickness, and total scores, and histologically enhanced epidermal thickening, hyperkeratosis, and dermal inflammatory infiltrates, including Ly6G+ neutrophils and CD3+ T cells. HSD increased mRNA levels of Il17a, Il22, Tnfa, Il1b, Il23a, Il23r, Cxcl1, Ccl20, Krt16, and Ccnd1 in IMQ-induced dermatitis. HSD increased the immunostaining areas of whole and Ser 422-phosphorylated forms of serum- and glucocorticoid-inducible kinase 1 (SGK1) in epidermal keratinocytes and dermal-infiltrating cells in IMQ-induced dermatitis. Intraperitoneal SGK1 inhibitor EMD638683 reversed the above effects of HSD in exacerbating IMQ-induced dermatitis. Our present results indicate that HSD may exacerbate murine IMQ-induced psoriasis-like dermatitis at least partially through the activation of SGK1.