Biomolecules & Therapeutics

  • 제29권5호
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  • Pages.492-497
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  • 2021
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  • 1976-9148(pISSN)
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  • 2005-4483(eISSN)
한국응용약물학회 (The Korean Society of Applied Pharmacology)
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Suppressive Effect of CYM50358 S1P4 Antagonist on Mast Cell Degranulation and Allergic Asthma in Mice

  • 투고 : 2020.11.12
  • 심사 : 2021.01.06
  • 발행 : 2021.09.01
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초록

Levels of sphingosine 1-phosphate (S1P), an intercellular signaling molecule, reportedly increase in the bronchoalveolar lavage fluids of patients with asthma. Although the type 4 S1P receptor, S1P4 has been detected in mast cells, its functions have been poorly investigated in an allergic asthma model in vivo. S1P4 functions were evaluated following treatment of CYM50358, a selective antagonist of S1P4, in an ovalbumin-induced allergic asthma model, and antigen-induced degranulation of mast cells. CYM50358 inhibited antigen-induced degranulation in RBL-2H3 mast cells. Eosinophil accumulation and an increase of Th2 cytokine levels were measured in the bronchoalveolar lavage fluid and via the inflammation of the lungs in ovalbumin-induced allergic asthma mice. CYM50358 administration before ovalbumin sensitization and before the antigen challenge strongly inhibited the increase of eosinophils and lymphocytes in the bronchoalveolar lavage fluid. CYM50358 administration inhibited the increase of IL-4 cytokines and serum IgE levels. Histological studies revealed that CYM50358 reduced inflammatory scores and PAS (periodic acid-Schiff)-stained cells in the lungs. The pro-allergic functions of S1P4 were elucidated using in vitro mast cells and in vivo ovalbumin-induced allergic asthma model experiments. These results suggest that S1P4 antagonist CYM50358 may have therapeutic potential in the treatment of allergic asthma.

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과제정보

This research was supported by the Basic Research Laboratory Program (BRL) and the Basic Science Research Program of the Korean National Research Foundation funded by the Korean Ministry of Science, ICT and Future Planning (NRF-2020R1A4A1016142 and NRF-2019R1A2C1005523).

참고문헌

  1. Allende, M. L., Bektas, M., Lee, B. G., Bonifacino, E., Kang, J., Tuymetova, G., Chen, W., Saba, J. D. and Proia, R. L. (2011) Sphingosine-1-phosphate lyase deficiency produces a pro-inflammatory response while impairing neutrophil trafficking. J. Biol. Chem. 286, 7348-7358. https://doi.org/10.1074/jbc.M110.171819
  2. Ammit, A. J., Hastie, A. T., Edsall, L. C., Hoffman, R. K., Amrani, Y., Krymskaya, V. P., Kane, S. A., Peters, S. P., Penn, R. B., Spiegel, S. and Panettieri, R. A., Jr. (2001) Sphingosine 1-phosphate modulates human airway smooth muscle cell functions that promote inflammation and airway remodeling in asthma. FASEB J. 15, 1212-1214. https://doi.org/10.1096/fj.00-0742fje
  3. Brown, J., Wilson, T. and Metcalfe, D. (2008) The mast cell and allergic diseases: role in pathogenesis and implications for therapy. Clin. Exp. Allergy 38, 4-18. https://doi.org/10.1111/j.1365-2222.2007.02886.x
  4. Chiba, Y., Suzuki, K., Kurihara, E., Uechi, M., Sakai, H. and Misawa, M. (2010) Sphingosine-1-phosphate aggravates antigen-induced airway inflammation in mice. Open Respir. Med. J. 4, 82-85. https://doi.org/10.2174/1874306401004010082
  5. Choi, O. H., Kim, J.-H. and Kinet, J.-P. (1996) Calcium mobilization via sphingosine kinase in signalling by the FcɛRI antigen receptor. Nature 380, 634-636. https://doi.org/10.1038/380634a0
  6. Dillmann, C., Mora, J., Olesch, C., Brune, B. and Weigert, A. (2015) S1PR4 is required for plasmacytoid dendritic cell differentiation. Biol. Chem. 396, 775-782. https://doi.org/10.1515/hsz-2014-0271
  7. Dillmann, C., Ringel, C., Ringleb, J., Mora, J., Olesch, C., Fink, A. F., Roberts, E., Brune, B. and Weigert, A. (2016) S1PR4 signaling attenuates ILT 7 internalization to limit IFN-alpha production by human plasmacytoid dendritic cells. J. Immunol. 196, 1579-1590. https://doi.org/10.4049/jimmunol.1403168
  8. Fettel, J., Kuhn, B., Guillen, N. A., Surun, D., Peters, M., Bauer, R., Angioni, C., Geisslinger, G., Schnutgen, F., Meyer Zu Heringdorf, D., Werz, O., Meybohm, P., Zacharowski, K., Steinhilber, D., Roos, J. and Maier, T. J. (2019) Sphingosine-1-phosphate (S1P) induces potent anti-inflammatory effects in vitro and in vivo by S1P receptor 4-mediated suppression of 5-lipoxygenase activity. FASEB J. 33, 1711-1726. https://doi.org/10.1096/fj.201800221R
  9. Gilfillan, A. M., Peavy, R. D. and Metcalfe, D. D. (2009) Amplification mechanisms for the enhancement of antigen-mediated mast cell activation. Immunol. Res. 43, 15-24. https://doi.org/10.1007/s12026-008-8046-9
  10. Graler, M. H., Bernhardt, G. and Lipp, M. (1998) EDG6, a novel G-protein-coupled receptor related to receptors for bioactive lysophospholipids, is specifically expressed in lymphoid tissue. Genomics 53, 164-169. https://doi.org/10.1006/geno.1998.5491
  11. Guerrero, M., Urbano, M., Zhao, J., Crisp, M., Chase, P., Hodder, P., Schaeffer, M. T., Brown, S., Rosen, H. and Roberts, E. (2012) Discovery, design and synthesis of novel potent and selective sphingosine-1-phosphate 4 receptor (S1P4-R) agonists. Bioorg. Med. Chem. Lett. 22, 537-542. https://doi.org/10.1016/j.bmcl.2011.10.096
  12. Heo, J. Y. and Im, D. S. (2019) Anti-allergic effects of salvianolic acid A and tanshinone IIA from Salvia miltiorrhiza determined using in vivo and in vitro experiments. Int. Immunopharmacol. 67, 69-77. https://doi.org/10.1016/j.intimp.2018.12.010
  13. Huang, J., Su, M., Lee, B. K., Kim, M. J., Jung, J. H. and Im, D. S. (2018) Suppressive effect of 4-hydroxy-2-(4-hydroxyphenethyl) isoindoline-1,3-dione on ovalbumin-induced allergic asthma. Biomol. Ther. (Seoul) 26, 539-545. https://doi.org/10.4062/biomolther.2018.006
  14. Jolly, P. S., Bektas, M., Olivera, A., Gonzalez-Espinosa, C., Proia, R. L., Rivera, J., Milstien, S. and Spiegel, S. (2004) Transactivation of sphingosine-1-phosphate receptors by FcɛRI triggering is required for normal mast cell degranulation and chemotaxis. J. Exp. Med. 199, 959-970. https://doi.org/10.1084/jem.20030680
  15. Khalaf, K., Paoletti, G., Puggioni, F., Racca, F., De Luca, F., Giorgis, V., Canonica, G. W. and Heffler, E. (2019) Asthma from immune pathogenesis to precision medicine. Semin. Immunol. 46, 101294. https://doi.org/10.1016/j.smim.2019.101294
  16. Kim, M. J. and Im, D. S. (2019) Suppressive effects of type I angiotensin receptor antagonists, candesartan and irbesartan on allergic asthma. Eur. J. Pharmacol. 852, 25-33. https://doi.org/10.1016/j.ejphar.2019.02.035
  17. Kulinski, J. M., Proia, R. L., Larson, E. M., Metcalfe, D. D. and Olivera, A. (2018) S1P(4) regulates passive systemic anaphylaxis in mice but is dispensable for canonical IgE-mediated responses in mast cells. Int. J. Mol. Sci. 19, 1279. https://doi.org/10.3390/ijms19051279
  18. Lee, B. K., Park, S. J., Nam, S. Y., Kang, S., Hwang, J., Lee, S. J. and Im, D. S. (2018) Anti-allergic effects of sesquiterpene lactones from Saussurea costus (Falc.) Lipsch. determined using in vivo and in vitro experiments. J. Ethnopharmacol. 213, 256-261. https://doi.org/10.1016/j.jep.2017.11.018
  19. Moffatt, M. F., Kabesch, M., Liang, L., Dixon, A. L., Strachan, D., Heath, S., Depner, M., von Berg, A., Bufe, A. and Rietschel, E. (2007) Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma. Nature 448, 470-473. https://doi.org/10.1038/nature06014
  20. Onuma, T., Tanabe, K., Kito, Y., Tsujimoto, M., Uematsu, K., Enomoto, Y., Matsushima-Nishiwaki, R., Doi, T., Nagase, K., Akamatsu, S., Tokuda, H., Ogura, S., Iwama, T., Kozawa, O. and Iida, H. (2017) Sphingosine 1-phosphate (S1P) suppresses the collagen-induced activation of human platelets via S1P4 receptor. Thromb. Res. 156, 91-100. https://doi.org/10.1016/j.thromres.2017.06.001
  21. 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 S1P2 axis in anaphylaxis and pulmonary edema. J. Exp. Med. 207, 465-474. https://doi.org/10.1084/jem.20091513
  22. 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
  23. Park, S. J. and Im, D. S. (2019) 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
  24. Park, S. J. and Im, D. S. (2020) Blockage of sphingosine-1-phosphate receptor 2 attenuates 2,4-dinitrochlorobenzene-induced atopic dermatitis in mice. Acta Pharmacol. Sin. 41, 1487-1496. https://doi.org/10.1038/s41401-020-0412-8
  25. Prieschl, E. E., Csonga, R., Novotny, V., Kikuchi, G. E. and Baumruker, T. (1999) The balance between sphingosine and sphingosine1-phosphate is decisive for mast cell activation after Fcɛ receptor I triggering. J. Exp. Med. 190, 1-8. https://doi.org/10.1084/jem.190.1.1
  26. Prussin, C. and Metcalfe, D. D. (2003) 4. IgE, mast cells, basophils, and eosinophils. J. Allergy Clin. Immunol. 111, S486-S494. https://doi.org/10.1067/mai.2003.120
  27. Romagnani, S. (2002) Cytokines and chemoattractants in allergic inflammation. Mol. Immunol. 38, 881-885. https://doi.org/10.1016/S0161-5890(02)00013-5
  28. Roviezzo, F., Di Lorenzo, A., Bucci, M., Brancaleone, V., Vellecco, V., De Nardo, M., Orlotti, D., De Palma, R., Rossi, F., D'Agostino, B. and Cirino, G. (2007) Sphingosine-1-phosphate/sphingosine kinase pathway is involved in mouse airway hyperresponsiveness. Am. J. Respir. Cell Mol. Biol. 36, 757-762. https://doi.org/10.1165/rcmb.2006-0383OC
  29. Saluja, R., Kumar, A., Jain, M., Goel, S. K. and Jain, A. (2017) Role of sphingosine-1-phosphate in mast cell functions and asthma and its regulation by non-coding RNA. Front. Immunol. 8, 587. https://doi.org/10.3389/fimmu.2017.00587
  30. Schulze, T., Golfier, S., Tabeling, C., Rabel, K., Graler, M. H., Witzenrath, M. and Lipp, M. (2011) Sphingosine-1-phospate receptor 4 (S1P4) deficiency profoundly affects dendritic cell function and TH17-cell differentiation in a murine model. FASEB J. 25, 4024-4036. https://doi.org/10.1096/fj.10-179028
  31. Tagaya, E. and Tamaoki, J. (2007) Mechanisms of airway remodeling in asthma. Allergol. Int. 56, 331-340. https://doi.org/10.2332/allergolint.R-07-152
  32. Van Rijt, L. S. and Lambrecht, B. (2005) Dendritic cells in asthma: a function beyond sensitization. Clin. Exp. Allergy 35, 1125-1134. https://doi.org/10.1111/j.1365-2222.2005.02321.x
  33. Worgall, T. S. (2017) Sphingolipids, ORMDL3 and asthma: what is the evidence? Curr. Opin. Clin. Nutr. Metab. Care 20, 99-103. https://doi.org/10.1097/MCO.0000000000000349

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