Biomol Ther.  2020 Nov;28(6):537-541. 10.4062/biomolther.2020.036.

Topical Application of S1P₂ Antagonist JTE-013 Attenuates 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis in Mice

• Kang J
• Lee JH
• Im DS

• KMID: 2508208
• DOI: http://doi.org/10.4062/biomolther.2020.036

Abstract

Sphingosine-1-phosphate (S1P) and its receptors have been implicated in atopic dermatitis. S1P₂ was found to function as a proallergic receptor, while its antagonist JTE-013 was found to suppress allergic asthma in mice. Topical application of JTE-013 has not been investigated in an in vivo model of atopic dermatitis. Therefore, the therapeutic potential of JTE-013 topical application was evaluated by the use of a 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis mouse model. DNCB-induced inflammation and mast cell accumulation in skin tissues were significantly suppressed by topical JTE-013 treatment in BALB/c mice. DNCB-induced increase of lymph nodes sizes and elevated inflammatory cytokines (IL-4, IL-13, IL-17, and IFN-γ) in lymph nodes were also significantly reduced by the JTE-013 treatment. Elevated serum levels of IgE were significantly suppressed by the topical treatment of JTE-013. In summary, the topical treatment of JTE-013 S1P₂antagonist suppressed DNCB-induced atopic dermatitis symptoms and immune responses. These results suggested JTE-013 as a potential therapeutic agent for atopic dermatitis.

Keyword

Atopy; Dermatitis; Dendritic cell; Sphingosine 1-phosphate; S1P₂