Topical Application of S1P(2) Antagonist JTE-013 Attenuates 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis in Mice

Sphingosine-1-phosphate (S1P) and its receptors have been implicated in atopic dermatitis. S1P(2) was found to function as a pro-allergic 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 S1P(2) antagonist suppressed DNCB-induced atopic dermatitis symptoms and immune responses. These results suggested JTE-013 as a potential therapeutic agent for atopic dermatitis.