KSBB Journal

  • 제29권1호
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  • Pages.36-41
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  • 2014
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  • 1225-7117(pISSN)
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  • 2288-8268(eISSN)
한국생물공학회 (The Korean Society for Biotechnology and Bioengineering)
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N,N,N-Trimethylphytosphingosine (TMP)의 염증성 피부질환 치료제 가능성에 관한 연구

Study for Possibility of N,N,N-Trimethylphytosphingosine (TMP) for Management of Chronic Skin Diseases

  • Seo, Won-Sang (Department of Microbial Engineering, Konkuk University) ;
  • Oh, Han-Na (Charmzone R&D Center, Charmzone Cosmetic, Ltd.) ;
  • Park, Woo-Jung (Charmzone R&D Center, Charmzone Cosmetic, Ltd.) ;
  • Um, Sang-Young (Charmzone R&D Center, Charmzone Cosmetic, Ltd.) ;
  • Kang, Sang-Mo (Department of Microbial Engineering, Konkuk University)
  • 투고 : 2013.12.16
  • 심사 : 2014.01.22
  • 발행 : 2014.02.27
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초록

Skin disease is one of the most common diseases and its incidence is increasing dramatically in modern society. Specially, many attempts have been made to treat chronic skin inflammation diseases, such as psoriasis and atopic dermatitis, but effective therapies for the immune cell-mediated skin diseases, including psoriasis and atopic dermatitis have not been developed. Until recently, several drug candidates which were claimed to be effective for skin diseases have been reported, but most of them are not used to treat chronic skin disease. Especially, Psoriasis is characterized by excessive growth and aberrant differentiation of keratinocytes, but is fully reversible with appropriate therapy. The trigger of the keratinocyte response is thought to be activation of the cellular immune system, with T cells and various immune-related cytokines. Formation of new blood vessels starts with early psoriatic changes and disappears with disease clearance. Several angiogenic mediators are up-regulated in psoriasis development. Contact- and mediator-dependent factors derived from keratinocytes, mast cells and immune cells may contribute to the strong blood vessel formation of psoriasis. New technologies and experimental models provide new insights into the role of angiogenesis in psoriasis pathogenesis. TMP and its derivatives themselves effectively inhibited in vitro cell migration, tube formation, and the expression of angiogenic factors. However, TMP and its derivatives induced side effects including hemolysis and local side effects. Therefore, in an attempt to reduce the toxicity and the undesirable side effects of TMP and derivatives, a liposomal formulation was prepared and tested for its effectiveness. TMP and derivatives liposomes retained the effectiveness of TMP in vitro while side effects were reduced. These results support the conclusion that TMP effectively inhibits in vitro angiogenesis, with the possibility that use as a psoriasis relief agent.

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참고문헌

  1. Folkman, J. (1971) Tumor angiogenesis: therapeutic implications. N. Engl. J. Med. 285: 1182-1186. https://doi.org/10.1056/NEJM197111182852108
  2. Ossowski, L. and E. Reich (1983) Antibodies to plasminogen activator inhibit human tumor metastasis. Cell 35: 611-619. https://doi.org/10.1016/0092-8674(83)90093-4
  3. Holash, J., S. J. Wiegand, and G. D. Yancopoulos (1999) New model of tumor angiogenesis: Dynamic balance between vessel regression and growth mediated by angiopoietins and VEGF. Oncogene 18: 5356-5362. https://doi.org/10.1038/sj.onc.1203035
  4. Hood, J. D., M. Bednarski, R. Frausto, S. Guccione, R. A. Reisfeld, R. Xiang, and D. A. Cheresh (2002) Tumor regression by targeted gene delivery to the neovasculature. Science 296: 2404-2407. https://doi.org/10.1126/science.1070200
  5. Weidner, N., P. R. Carroll, J. Flax, W. Blumenfeld, and J. Folkman (1993) Tumor angiogenesis correlates with metastasis in invasive prostate carcinoma. Am. J. Pathol. 143: 401-409.
  6. Merrill, A. H. (2002) Sphingolipids: Metabolism and cell signaling. New Compr. Biochem. 36: 373-407. https://doi.org/10.1016/S0167-7306(02)36016-2
  7. Spiegel, S. and A. H. Merrill, Jr. (1996) Sphingolipid metabolism and cell growth regulation. FASEB J. 10: 1388-1397. https://doi.org/10.1096/fasebj.10.12.8903509
  8. Spiegel, S. and S. Milstien (2002) Sphingosine 1-phosphate, a key cell signaling molecule. J. Biol. Chem. 277: 25851-25854. https://doi.org/10.1074/jbc.R200007200
  9. Woodcock, J. (2006) Sphingosine and ceramide signalling in apoptosis. IUBMB Life 58: 462-466. https://doi.org/10.1080/15216540600871118
  10. Park, S. R., H. J. Cho, K. J. Moon, K. H. Chun, S. Y. Kong, S. S. Yoon, J. S. Lee, and S. Park (2010) Cytotoxic effects of novel phytosphingosine derivatives, including N,Ndimethylphytosphingosine and N-monomethylphytosphingosine, in human leukemia cell line HL60. Leuk. Lymphoma 51: 132-145. https://doi.org/10.3109/10428190903383419
  11. Song, C. K., S. H. Jung, D. D. Kim, K. S. Jeong, B. C. Shin, and H. Seong (2009) Disaccharidemodified liposomes and their in vitro intracellular uptake. Int. J. Pharm. 380: 161-169. https://doi.org/10.1016/j.ijpharm.2009.07.014
  12. Park, Y. S., S. Hakomori, S. Kawa, F. Ruan, and Y. Igarashi (1994) Liposomal N,N,Ntrimethylsphingosine (TMS) as an inhibitor of B16 melanoma cell growth and metastasis with reduced toxicity and enhanced drug efficacy compared to free TMS: Cell membrane signaling as a target in cancer therapy III. Cancer Res. 54: 2213-2217.
  13. Gabizon, A., A. Dagan, D. Goren, Y. Barenholz, and Z. Fuks (1982) Liposomes as in vivo carriers of adriamycin: Reduced cardiac uptake and preserved antitumor activity in mice. Cancer Res. 42: 4734-4739.
  14. Gabizon, A. A. (1995) Liposome circulation time and tumor targeting: implications for cancer chemotherapy. Adv. Drug Deliv. Rev. 16: 285-294. https://doi.org/10.1016/0169-409X(95)00030-B
  15. Matsuo, H., M. Wakasugi, H. Takanaga, H. Ohtani, M. Naito, T. Tsuruo, and Y. Sawada (2001) Possibility of the reversal of multidrug resistance and the avoidance of side effects by liposomes modified with MRK-16. A monoclonal antibody to P-glycoprotein. J. Control. Release 77: 77-86. https://doi.org/10.1016/S0168-3659(01)00460-6
  16. Song, C. K., J. H. Lee, A. Jahn, M. J. Choi, S. K. Namgoong, S. S. Hong, S. Chong, C. K. Shim, S. J. Chung, and D. D. Kim (2012) In vitro and in vivo evaluation of N,N,N-trimethylphytosphingosine- iodide (TMP) in liposomes for the treatment of angiogenesis and metastasis. Int J Pharm. 434: 191-198. https://doi.org/10.1016/j.ijpharm.2012.05.042
  17. Namgoong, S. K. and S. Y. Park (2003) Phytosphingosine derivatives with antitumor activity. US Patent 6,538,032.
  18. Garca-Caballero, M., M. Mar-Beffa , M. . Medina, and A. R. Quesada (2011) Dimethylfumarate inhibits angiogenesis in vitro and in vivo: a possible role for its antipsoriatic effect? J Invest Dermatol. 131: 1347-55. https://doi.org/10.1038/jid.2010.416
  19. Huang A. J., M. B. Furie, S. C. Nicholson, J. Fischbarg, L. S. Liebovitch, and S. C. Silverstein (1988) Effects of human neutrophil chemotaxis across human endothelial cell monolayers on the permeability of these monolayers to ions and macromolecules. J Cell Physiol. 135: 355-366. https://doi.org/10.1002/jcp.1041350302

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