Evaluation of the Anti-inflammatory and Immunomodulatory Effects of BSASM Using in vitro Experiments

시험관내에서 천연물제제 BSASM의 항염증 및 면역억제 효능 평가

  • 이종성 (바이오스펙트럼 생명과학연구소) ;
  • 박유미 (바이오스펙트럼 생명과학연구소) ;
  • 박병화 (바이오스펙트럼 생명과학연구소) ;
  • 정광선 (바이오스펙트럼 생명과학연구소) ;
  • 김국현 (바이오스펙트럼 생명과학연구소) ;
  • 이원희 (녹십자 R&D) ;
  • 박덕훈 (바이오스펙트럼 생명과학연구소)
  • Published : 2003.09.30

Abstract

For effective management of atopic dermatitis, it is important to introduce a therapeutic agent although having the fewest side effects, has the greatest anti- inflammatory effect. In the course of screening anti-inflammatory agents, we obtained BSASM composed of several plant extracts. This study was designed to investigate anti-inflammatory and immunomodulatory effects of BSASM. As a first step, $NF-{\kappa}B$ luciferase reporter assay was performed to know the involvement of BSASM in the production of proinflammatory cytokines because $NF-{\kappa}B$ element has been known to play a major role in expression of cytokine genes such as interleukin-8 (IL-8) or tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})$. LPS (lipolysaccharide)-induced $NF-{\kappa}B$ activation was inhibited by BSASM. In addition, we found the fact that BSASM inhibits LPS-induced produced production of IL-8 and $TNF-{\alpha}$ proinflammatory cytokines, indicating BSASM has anti-inflammatory effect. In interleukin-2 (IL-2) luciferase reporter assay in Jurkat T cells, BSASM reduced PHA (Phytohemagglutinin)-induced IL-2 luciferase activity, suggesting the possibility that BSASM might also have an immunomodulatory function in T cell-mediated immune response. Based on these results, we suggest the possibility that BSASM can be introduced to improve symptom of immune-related skin diseases, namely, atopic dermatitis.

Keywords

References

  1. Cooper, K. D. (1994) Atopic dermatitis: recent trends in pathogenesis and therapy J. Invest. Dermatol. 102: 128-137 https://doi.org/10.1111/1523-1747.ep12371746
  2. Bos, J. D. Wierenga, O., Si1levis, J. H., Heijden, F. L., and Kapsenberg, M. L. (1992) Immune dysregulation in atopic eczema. Arch. Dermatol. 128: 1509-1512 https://doi.org/10.1001/archderm.128.11.1509
  3. Mosmann, T. R., Cherwinski, H., Bond, M. W., Giedlin, M. A., and Coffman, R. L. (1986) Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins., J. Immunol. 136: 2348-2357
  4. 이성훈, 이주홍, 이승철, 김영근 (1998) 아토피 피부염 환자의 중증도 지표로서의 혈청 InterLeukin-4에 관한 연구. 대피지 36: 95-102
  5. Venge, P. (1993) Eosinophil and neutrophil granulocytes. Allergy. 36: 95-102
  6. Ackerman, S. J., Loegering, D. A., Venge, P., Olsson, I., Harley, J. B., and Fauci, A. S. (1983) Distinctive cationic proteins of the human eosinophil granule: major basic protein, eosinophil cationic protein, and eosinophil-derived neurotoxin., J. Immunol. 131: 2977-2982
  7. Czech, W., Schopf, E., and Kapp, A. (1996) Soluble Eselectin in sera of patients with atopic dermatitis and psoriasis-correlation with disease activity. Br. J. Dermatol. 134: 17-21 https://doi.org/10.1111/j.1365-2133.1996.tb07833.x
  8. Baumann, L., Kerdel, F. Freedberg, I. M., Eisen, A. Z., Wolff, K., Austin, K. F., Goldsmith, L. A., Katz, S. I., and Fitzpatrick, T. B. (1999) Dermatology in general medicine. (5th ed.), 2713-2717. Academic Press, New York, NY
  9. Robinson, N., Singri, P., and Gordon, K. M. (2001) Safety of the new macrolide immunomodulators. Semin Cutan Med Surg. 20(4): 242-249 https://doi.org/10.1053/sder.2001.29063
  10. Vender, R. B. (2002) ltemative treatments for atopic dermatitis: A selected review. Skin Therapy Lett. 7(2): 1-5
  11. Tanaka, S., Yoichi, S., Ao, L., Matumoto, M., Morimoto, K., Akimoto, N., Honda, G., Tabata, M., Oshima, T.,Masuda, T., Asmawi, M. Z., Ismail, Z., Yusof, S. M., Din, L. B., and Said, I. M. (2001) Potential immunosuppressive and antiinflammatory activities of malaysian medicinal plants characterized by reduced cell surface expression of cell adhesion molecules. Phytother Res. 15(8): 681-686 https://doi.org/10.1002/ptr.778
  12. Miescher, S. M. and Vogel, M. (2002) Molecular aspects of allergy. Mol. Aspects Med. 23(6): 413-462 https://doi.org/10.1016/S0098-2997(02)00009-2
  13. Li, M. Y., Ryan, P., and Batey, R. G. (2003) Traditional Chinese medicine prevents intlammation in $CCI_4$-related liver injury in mice. Am. J. Chin. Med. 31(1): 119-127 https://doi.org/10.1142/S0192415X03000680
  14. Yuan, R. and Lin, Y. (2000) Traditional Chinese medicine: an approach to scientific proof and clinical validation. Pharmacol. Ther. 86(2): 191-198 https://doi.org/10.1016/S0163-7258(00)00039-5
  15. Li, M. Y., Ryan, P., and Batey, R. G. (2003) Traditional Chinese medicine prevents intlammation in $CC1_4$-related liver injury in mice. Am. J. Chin. Med. 31(1): 119-127 https://doi.org/10.1142/S0192415X03000680
  16. Young, B. C., Chan, K. K., and Yungdae, Y. (1999) An adapter protein interacting with the SH2 domain of p56lck , is required for T cell activation. J. Immunol. 163: 5242-5249
  17. Benjamin, R. V., Shijun, Y., and James, J. L. (1995) Induction of proinflammatory cytokines by a soluble factor of Propionibacterium acnes. Infection and Immunity. 63: 3158-3165
  18. Zheng-Ming, W., Chao, L., and Roman Dziarski. (2000) Chemokines are the main proinflammatory mediators in human monocytes activated by Staphylococcus aureus, peptidoglycan, and endotoxin. J. Biol. Chem. 275(27): 20260-20267 https://doi.org/10.1074/jbc.M909168199
  19. Jain, A. and Basal, E. (2003) Inhibition of Propionibacterium acnes-induced mediators of inflammation by Indian herbs. Phytomedicine 10: 34-38 https://doi.org/10.1078/094471103321648638
  20. Benjamin, R., Vowels, S. Y., and James, J. L. (1995) Induction of proinflammatory cytokines by. a soluble factor of Propionibacterium acnes: Implication for chronic inflammatory acne. Infection and Immunity 63(8): 3158-3165
  21. Naofumi, M., Shu-ichi, O., Yuji, I., and Kouji, M. (1994) Molecular mechanism of interleukin-8 gene expression. J. Leukocyte Biology 56: 554-558
  22. Anderson, S. J. and Perlmutter, R. M. (1995) A signaling pathway governing early thymocyte maturation. Immunol. Today 16: 99-105 https://doi.org/10.1016/0167-5699(95)80096-4
  23. Molina, T. J., Kishihara, K., Siderovski, D. P, van Ewijk, W., Narendran, A., Timms, E., Wakeham, A., Paige, C. J., Hartmann, K. U., and Veillette, A. (1992) Profound block in thymocyte development in mice lacking p56lck. Nature 357: 161-164 https://doi.org/10.1038/357161a0
  24. Hatakeyama, M., Kono, T., Kobayashi, N., Kawahara, A, Levin, S. D., Perlmutter, R. M., and Taniguchi, T. (1991) Interaction of the IL-2 receptor with the src-family kinase p56lck : identification of novel intermolecular association. Science 252: 1523-1528 https://doi.org/10.1126/science.2047859
  25. Minami, Y., Kono, T., Yamada, K., Kobayashi, N., Kawahara, A., Perlmutter, R. M., and Taniguchi, T. (1993) Association of p56lck with IL-2 receptor beta chain is critical for the IL-2induced activation of p56lck. EMBO J. 12: 759-768
  26. Marth, J. D., Cooper, J. A., King, C. S., Ziegler, S. F., Tinker, D. A., Overell, R. W., Krebs, E. G., and Perlmutter, R. M. (1988) Neoplastic transformation induced by an activated 1lymphocyte-speciific protein tyrosne kinase (p56lck).mol. Cell. BioI. 8: 540-550
  27. Jongsung, L., Byunghwa P, Kwangseon, 1., Kukhyun K., Kyu, H. K., and Deokhoon P. (2003) Evaluation of the antiintlanunatory and atopic dermatitis-mitigating effects of BSASM. Acta Derm Venereol. (submitted)