Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Topical Application of S1P2 Antagonist JTE-013 Attenuates 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis in Mice

  • Kang, Jisoo (Laboratory of Pharmacology, College of Pharmacy, Pusan National University) ;
  • Lee, Ju-Hyun (Laboratory of Pharmacology, College of Pharmacy, and Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University) ;
  • Im, Dong-Soon (Laboratory of Pharmacology, College of Pharmacy, Pusan National University)
  • Received : 2020.03.06
  • Accepted : 2020.04.29
  • Published : 2020.11.01
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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 S1P2 antagonist suppressed DNCB-induced atopic dermatitis symptoms and immune responses. These results suggested JTE-013 as a potential therapeutic agent for atopic dermatitis.

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References

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