DOI QR코드

DOI QR Code

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)
  • 투고 : 2020.03.06
  • 심사 : 2020.04.29
  • 발행 : 2020.11.01

초록

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.

키워드

참고문헌

  1. Baumer, W., Rossbach, K., Mischke, R., Reines, I., Langbein-Detsch, I., Luth, A. and Kleuser, B. (2011) Decreased concentration and enhanced metabolism of sphingosine-1-phosphate in lesional skin of dogs with atopic dermatitis: disturbed sphingosine-1-phosphate homeostasis in atopic dermatitis. J. Invest. Dermatol. 131, 266-268. https://doi.org/10.1038/jid.2010.252
  2. Bock, S., Pfalzgraff, A. and Weindl, G. (2016) Sphingosine 1-phospate differentially modulates maturation and function of human Langerhans-like cells. J. Dermatol. Sci. 82, 9-17. https://doi.org/10.1016/j.jdermsci.2016.01.002
  3. Checa, A., Xu, N., Sar, D. G., Haeggstrom, J. Z., Stahle, M. and Wheelock, C. E. (2015) Circulating levels of sphingosine-1-phosphate are elevated in severe, but not mild psoriasis and are unresponsive to anti-TNF-a treatment. Sci. Rep. 5, 12017. https://doi.org/10.1038/srep12017
  4. Japtok, L., Schaper, K., Baumer, W., Radeke, H. H., Jeong, S. K. and Kleuser, B. (2012) Sphingosine 1-phosphate modulates antigen capture by murine Langerhans cells via the S1P2 receptor subtype. PLoS ONE 7, e49427. https://doi.org/10.1371/journal.pone.0049427
  5. Jeong, S. K., Kim, Y. I., Shin, K. O., Kim, B. W., Lee, S. H., Jeon, J. E., Kim, H. J., Lee, Y. M., Mauro, T. M., Elias, P. M., Uchida, Y. and Park, K. (2015) Sphingosine kinase 1 activation enhances epidermal innate immunity through sphingosine-1-phosphate stimulation of cathelicidin production. J. Dermatol. Sci. 79, 229-234. https://doi.org/10.1016/j.jdermsci.2015.06.007
  6. Kim, D. S., Kim, S. Y., Kleuser, B., Schafer-Korting, M., Kim, K. H. and Park, K. C. (2004) Sphingosine-1-phosphate inhibits human keratinocyte proliferation via Akt/protein kinase B inactivation. Cell. Signal. 16, 89-95. https://doi.org/10.1016/S0898-6568(03)00114-1
  7. Kim, J. Y., Jeong, M. S., Park, M. K., Lee, M. K. and Seo, S. J. (2014) Time-dependent progression from the acute to chronic phases in atopic dermatitis induced by epicutaneous allergen stimulation in NC/Nga mice. Exp. Dermatol. 23, 53-57. https://doi.org/10.1111/exd.12297
  8. Koga, C., Kabashima, K., Shiraishi, N., Kobayashi, M. and Tokura, Y. (2008) Possible pathogenic role of Th17 cells for atopic dermatitis. J. Invest. Dermatol. 128, 2625-2630. https://doi.org/10.1038/jid.2008.111
  9. Kohno, T., Tsuji, T., Hirayama, K., Watabe, K., Matsumoto, A., Kohno, T. and Fujita, T. (2004) A novel immunomodulator, FTY720, prevents spontaneous dermatitis in NC/Nga mice. Biol. Pharm. Bull. 27, 1392-1396. https://doi.org/10.1248/bpb.27.1392
  10. Leong, W. I. and Saba, J. D. (2010) S1P metabolism in cancer and other pathological conditions. Biochimie 92, 716-723. https://doi.org/10.1016/j.biochi.2010.02.014
  11. Muraro, A., Lemanske, R. F., Jr., Hellings, P. W., Akdis, C. A., Bieber, T., Casale, T. B., Jutel, M., Ong, P. Y., Poulsen, L. K., Schmid-Grendelmeier, P., Simon, H. U., Seys, S. F. and Agache, I. (2016) Precision medicine in patients with allergic diseases: airway diseases and atopic dermatitis-PRACTALL document of the European Academy of Allergy and Clinical Immunology and the American Academy of Allergy, Asthma & Immunology. J. Allergy Clin. Immunol. 137, 1347-1358. https://doi.org/10.1016/j.jaci.2016.03.010
  12. Mysliwiec, H., Baran, A., Harasim-Symbor, E., Choromanska, B., Mysliwiec, P., Milewska, A. J., Chabowski, A. and Flisiak, I. (2017) Increase in circulating sphingosine-1-phosphate and decrease in ceramide levels in psoriatic patients. Arch. Dermatol. Res. 309, 79-86. https://doi.org/10.1007/s00403-016-1709-9
  13. Nakashima, D., Kabashima, K., Sakabe, J., Sugita, K., Kobayashi, T., Yoshiki, R. and Tokura, Y. (2008) Impaired initiation of contact hypersensitivity by FTY720. J. Invest. Dermatol. 128, 2833-2841. https://doi.org/10.1038/jid.2008.174
  14. Olivera, A., Dillahunt, S. E. and Rivera, J. (2013) Interrogation of sphingosine-1-phosphate receptor 2 function in vivo reveals a prominent role in the recovery from IgE and IgG-mediated anaphylaxis with minimal effect on its onset. Immunol. Lett. 150, 89-96. https://doi.org/10.1016/j.imlet.2013.01.005
  15. Oskeritzian, C. A., Price, M. M., Hait, N. C., Kapitonov, D., Falanga, Y. T., Morales, J. K., Ryan, J. J., Milstien, S. and Spiegel, S. (2010) Essential roles of sphingosine-1-phosphate receptor 2 in human mast cell activation, anaphylaxis, and pulmonary edema. J. Exp. Med. 207, 465-474. https://doi.org/10.1084/jem.20091513
  16. Park, S. J. and Im, D. S. (2017) Sphingosine 1-phosphate receptor modulators and drug discovery. Biomol. Ther. (Seoul) 25, 80-90. https://doi.org/10.4062/biomolther.2016.160
  17. Park, S. J. and Im, D. S. (2019a) Blockage of sphingosine-1-phosphate receptor 2 attenuates allergic asthma in mice. Br. J. Pharmacol. 176, 938-949. https://doi.org/10.1111/bph.14597
  18. Park, S. J. and Im, D. S. (2019b) Deficiency of sphingosine-1-phosphate receptor 2 (S1P2) attenuates bleomycin-induced pulmonary fibrosis. Biomol. Ther. (Seoul) 27, 318-326. https://doi.org/10.4062/biomolther.2018.131
  19. Prieschl, E. E., Csonga, R., Novotny, V., Kikuchi, G. E. and Baumruker, T. (1999) The balance between sphingosine and sphingosine-1-phosphate is decisive for mast cell activation after Fc epsilon receptor I triggering. J. Exp. Med. 190, 1-8. https://doi.org/10.1084/jem.190.1.1
  20. Proia, R. L. and Hla, T. (2015) Emerging biology of sphingosine-1-phosphate: its role in pathogenesis and therapy. J. Clin. Invest. 125, 1379-1387. https://doi.org/10.1172/JCI76369
  21. Reines, I., Kietzmann, M., Mischke, R., Tschernig, T., Luth, A., Kleuser, B. and Baumer, W. (2009) Topical application of sphingosine-1-phosphate and FTY720 attenuate allergic contact dermatitis reaction through inhibition of dendritic cell migration. J. Invest. Dermatol. 129, 1954-1962. https://doi.org/10.1038/jid.2008.454
  22. Schaper, K., Dickhaut, J., Japtok, L., Kietzmann, M., Mischke, R., Kleuser, B. and Baumer, W. (2013) Sphingosine-1-phosphate exhibits anti-proliferative and anti-inflammatory effects in mouse models of psoriasis. J. Dermatol. Sci. 71, 29-36. https://doi.org/10.1016/j.jdermsci.2013.03.006
  23. Spiegel, S. and Milstien, S. (2007) Functions of the multifaceted family of sphingosine kinases and some close relatives. J. Biol. Chem. 282, 2125-2129. https://doi.org/10.1074/jbc.R600028200
  24. Tsuji, T., Okuno, S., Kuroda, A., Hamazaki, J., Chikami, T., Sakurai, S., Yoshida, Y., Banno, R., Fujita, T. and Kohno, T. (2016) Therapeutic approach to mite-induced intractable dermatitis using novel immunomodulator FTY720 ointment (fingolimod) in NC/Nga mice. Allergol. Int. 65, 172-179. https://doi.org/10.1016/j.alit.2015.10.009
  25. Tsuji, T., Yoshida, Y., Iwatsuki, R., Inoue, M., Fujita, T. and Kohno, T. (2012) Therapeutic approach to steroid-resistant dermatitis using novel immunomodulator FTY720 (Fingolimod) in combination with betamethasone ointment in NC/Nga mice. Biol. Pharm. Bull. 35, 1314-1319. https://doi.org/10.1248/bpb.b12-00229
  26. Yanagawa, Y., Hoshino, Y., Kataoka, H., Kawaguchi, T., Ohtsuki, M., Sugahara, K. and Chiba, K. (1999) FTY720, a novel immunosuppressant, prolongs rat skin allograft survival by decreasing T-cell infiltration into grafts. Transplant. Proc. 31, 1227-1229. https://doi.org/10.1016/S0041-1345(98)01974-5

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