Regulatory Effects of Gamisamul-tang on Atopic Dermatitis Induced in the NC/Nga Mice

  • Yang, Sun-Sim (Department of Pathology, College of Oriental Medicine, Daejeon University) ;
  • NamGung, Uk (Department of Neurophysiology, College of Oriental Medicine, Daejeon University) ;
  • Kim, Dong-Hee (Department of Pathology, College of Oriental Medicine, Daejeon University)
  • Published : 2006.08.25

Abstract

The present study was conducted to investigate the effect of Gamisamul-tang (GSMT) on atopic dermatitis (AD). AD was induced in NC/Nga mutant mice by DNCB treatment. GSMT administration reduced levels of skin severity scores. Serum levels of IgE, IgG, IgM, and inflammatory cytokines including IL-4, IL-4 and 1L-13 were significantly decreased by GSMT treatment. Levels of mRNA's encoding IL-4, IL-6, IL-13, $TNF-{\alpha}$, and $interferon-{\gamma}$ in the dermal tissue and draining lymph node (DLN) by real time RT-PCR analysis showed decrease by GSMT testament. Moreover, the number of CD4+ and CD8+ cells was significantly decreased in the spleen and DLN tissues. Histological examination showed that infiltration levels of immune cells in ear, skin, and DLN of AD-induced NC/Nga mice were much improved by GSMT treatment. The present data suggest that GSMT may play an important role in recovering AD symptoms by regulating immune reactivity.

Keywords

References

  1. Beltrani, V.S. The Clinical spectrum of atopic dermatitis. J Allergy Clin Immunol 104, S87-98, 1999 https://doi.org/10.1016/S0091-6749(99)70050-3
  2. Braun-Falco, O., Plewig, G., Holff, H.H. and Winkelmann, R.K. Dermatology, Springer-Verlag, New York. p 348, 1991
  3. Leung, D.Y.M. Immunopathology of atopic dermatitis. Semin. Immunopathol. 13:427-440, 1992
  4. Wahlgren, C.F. Itch and atopic dermatitis: an overview. J Dermatol. 26:770-779, 1999 https://doi.org/10.1111/j.1346-8138.1999.tb02090.x
  5. Koblenzer, C.S. Itching and the atopic skin. J Allergy Clin Immunol 104, S109-1013, 1999 https://doi.org/10.1016/S0091-6749(99)70052-7
  6. Kay, A.B. Overview of allergy and allergic disease : with a view to the future. Br. Med. Bull. 56:843-864, 2000 https://doi.org/10.1258/0007142001903481
  7. Kondo, K., Nagami, T. and Teramoto, S. Differences in haematopoietic death among inbred strains of mice. In Bond, P.V. and Sugahara, T., eds, Comparative Cellular and Species Radiosensitivity, Igakushoin, Tokyo, p 20, 1969
  8. Matsuda, H., Watanabe, N., Geba, G.P., Sperl, J., Tsudzuki, M., Hiroi, J., Matsumoto, M., Ushio, H., Saito, S., Askenase, P.W., Ra, C. Development of atopic dermatitis-like skin lesion with IgE hyperproduction in NC/Nga mice. Int Immunol. 9:461-466, 1997 https://doi.org/10.1093/intimm/9.3.461
  9. Fujimaki, H., Nohara, K., Kobayashi, T., Suzuki, K., Eguchi-Kasai, K., Tsukumo, S., Kijima, M., Tohyama, C. Effect of a single oral dose of 2,3,7,8- tetrachlorodibenzo- p-dioxin on immune function in male NC/Nga mice. Toxicol Sci. 66:117-124, 2002 https://doi.org/10.1093/toxsci/66.1.117
  10. Hanifin, J. M. Atopic dermtitis. J. Am. Acad. Dermatol. 6:1-13, 1982 https://doi.org/10.1016/S0190-9622(82)70001-5
  11. Hara, J., Higuchi, K., Okamoto, R. Decreased levels of ceramides in involved and uninvolved skin of patients with AD. J Invest Dermatol 115:406-413, 2000 https://doi.org/10.1046/j.1523-1747.2000.00072.x
  12. Horan, R.F., Schneider, L.C. and Shetter, A.L. Allergic skin disorders and mastocytosis. J. Am. Med. Ass. 268:2858-2868, 1992 https://doi.org/10.1001/jama.268.20.2858
  13. Fleisher, Jr A.B. Treatment of atopic dermatitis: as a topical noncorticosteroidal therapy. J Allergy Clin Immunol. 104, S126-130, 1999 https://doi.org/10.1016/S0091-6749(99)70055-2
  14. Jun, J., Namgung, U., Kim, S.M., Kang, T.L., Kim, D.H. Inhibitory effects of Gamimahaenggamsuk-tang on RA-related inflammatory responses in cultured fibroblast-like synoviocytes. Korean J. Oriental Physiol. & Pathol. 19, 1647-1655, 2005
  15. Sakamoto, T., Miyazaki, E., Aramaki, Y., Arima, H., Takahashi, M., Kato, Y., Koga, M., Tsuchiya, S. Improvement of dermatitis by iontophoretically delivered antisense oligonucleotides for interleukin-10 in NC/Nga mice. Gene Ther. 11:317-324, 2004 https://doi.org/10.1038/sj.gt.3302171
  16. Sasagawa, T., Higashi, Y., Sakuma, S., Hirayama, Y., Sasagawa, Y., Ohkubo, Y., et al. Atopic dermatitis-like skin lesions induced by topical application of mite antigens in NC/Nga mice. Int Arch Allergy Immunol 126:239-247, 2001 https://doi.org/10.1159/000049520
  17. Larsen, F.S., Hanifin, J.M. Epidemiology of atopic dermatitis. Immunol Allergy Clinics NA 22:1-325, 2002
  18. Cookson, W.O., Moffatt, M.F. The genetics of atopic dermatitis. Curr. Opin. Allergy Clin. Immunol. 2:383-387, 2002 https://doi.org/10.1097/00130832-200210000-00003
  19. Suto, H., Matsuda, H., Mitsuishi, K., Hira, K., Uchida, T., Unno, T., Ogawa, H., Ra, C. NC/Nga mice: a mouse model for atopic dermatitis. Int Arch Allergy Immunol. 120 Suppl 1:70-75, 1999 https://doi.org/10.1159/000053599
  20. Novak, N., Bieber, T., and Leung, D.Y.M. Immune mechanisms leading to atopic dermatitis. J. Allergy Clin. Immunol. 112, S128-S139, 2003 https://doi.org/10.1016/j.jaci.2003.09.032
  21. Toda, M., Leung, D.Y., Molet, S., Boguniewicz, M., Taha, R., Christodoulopoulos, P., Fukuda, T., Elias, J.A., Hamid, Q.A. Polarized in vivo expression of IL-11 and IL-17 between acute and chronic skin lesions. J. Allergy Clin. Immunol. 111:875-881, 2003 https://doi.org/10.1067/mai.2003.1414
  22. Cherwinski, H.C., Schumacher, J.H., Brown, K.D. and Mosmann, T.R. Two types of mouse helper T cell clone: 3. Further differences in lymphokine synthesis between TH1 and TH2 clones revealed by RNA hybridization, functionally monospecific bioassays and monoclonal antibodies. J. Exp. Med. 166:1229-1244, 1987 https://doi.org/10.1084/jem.166.5.1229
  23. Mihm, M.C., Jr, Soter, N.A., Dvorak, H.F. and Austen, K.F. The structure of normal skin and the morphology of atopic eczema. J. Invest. Dermatol. 67:305-312, 1976 https://doi.org/10.1111/1523-1747.ep12514346
  24. Nassif, A., Chan, S.C., Storrs, F.J., Hanifin, J.M. Abnormal skin irritancy in atopic dermatitis and in atopy without dermatitis, Arch Dermatol. 130:1402-1407, 1994 https://doi.org/10.1001/archderm.130.11.1402
  25. Matsumoto, M., Kotani, M., Fujita, A., Higa, S., Kishimoto, T., Suemura, M., Tanaka, T. Oral administration of persimmon leaf extract ameliorates skin symptoms and transepidermal water loss in atopic dermatitis model mice, NC/Nga. Br J Dermatol. 146:221-227, 2002 https://doi.org/10.1046/j.1365-2133.2002.04557.x
  26. Gajewski, T.F. and Fitch, F.W. Anti-proliferative effect of IFN-g in immune regulation. I. IFN-gamma inhibits the proliferation of Th2 but not Th1 murine helper T lymphocyte clones. J. Immunol. 140:4245-4252, 1988
  27. Taniguchi, Y., Kohno, K., Inoue, S., Koya-Miyata, S., Okamoto, I., Arai, N., Iwaki, K., Ikeda, M., Kurimoto, M. Oral administration of royal jelly inhibits the development of atopicdermatitis-like skin lesions in NC/Nga mice. Int Immunopharmacol. 3:1313-1324, 2003 https://doi.org/10.1016/S1567-5769(03)00132-2
  28. Gao, X.K., Nakamura, N., Fuseda, K., Tanaka, H., Inagaki, N., Nagai, H. Establishment of allergic dermatitis in NC/Nga mice as a model for severe atopic dermatitis. Biol Pharm Bull. 27:1376-1381, 2004 https://doi.org/10.1248/bpb.27.1376