A Novel Model for Human Atopic Dermatitis: Application of Repeated DNCB Patch in BALB/c Mice, in Comparison with NC/Nga Mice

  • Lee, Kyoung-Sun (Department of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk University) ;
  • Jeong, Eui-Suk (Department of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk University) ;
  • Heo, Seung-Ho (Department of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk University) ;
  • Seo, Jin-Hee (Department of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk University) ;
  • Jeong, Dong-Gu (Department of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk University) ;
  • Choi, Yang-Kyu (Department of Laboratory Animal Medicine, College of Veterinary Medicine, Konkuk University)
  • Received : 2010.03.02
  • Accepted : 2010.03.17
  • Published : 2010.03.30

Abstract

The various murine models have contributed to the study of human atopic dermatitis (AD). However limitations of the models involve low reproducibility and long time to develop AD. In an attempt to overcome these limitations and establish an atopic dermatitis murine model, we repeated the application of 2, 4-dinitrochlorobenzene (DNCB) patch in NC/Nga and BALB/c mice, which has advantages in reproduction and cost. For the sensitization, a 1 $cm^2$ gauze-attached patch, where 1% or 0.2% DNCB was periodically attached on the back of NC/Nga and BALB/c mice. To estimate how homologous our model was with human atopic dermatitis, clinical, histological and immunological alterations were evaluated. Both strains showed severe atopic dermatitis, increase in subiliac lymph node weight, mast cells, epidermal hyperplasia and serum IgE levels. Though both exhibited a high IL-4/IFN-${\gamma}$ and IL-4/TNF-${\beta}$ ratio in the expression of mRNA, the shifting of DNCB-treated BALB/c mice was increased to more than double that of NC/Nga mice. These results suggest that our DNCB patched model using BALB/c mice were more suitable than NC/Nga mice in demonstrating the immune response. We anticipate that our novel model may be successfully used for pathogenesis of atopic dermatitis and assessment of therapeutic approaches.

Keywords

References

  1. Akdis, C.A., Akdis, M., Bieber, T., Bindslev-Jensen, C., Boguniewicz, M., Eigenmann, P., Hamid, Q., Kapp, A., Leung, D.Y., Lipozencic, J., Luger, T.A., Muraro, A., Novak, N., Platts-Mills, T.A., Rosenwasser, L., Scheynius, A., Simons, F.E., Spergel, J., Turjanmaa, K., Wahn, U., Weidinger, S., Werfel, T. and Zuberbier, T. (2006) Diagnosis and treatment of atopic dermatitis in children and adults: European Academy of Allergology and Clinical Immunology/American Academy of Allergy, Asthma and Immunology/PRACTALL Consensus Report. Allergy. 61, 969-987. https://doi.org/10.1111/j.1398-9995.2006.01153.x
  2. Chan, L.S., Robinson, N. and Xu, L. (2001) Expression of interleukin-4 in the epidermis of transgenic mice results in a pruritic inflammatory skin disease: an experimental animal model to study atopic dermatitis. J Invest Dermatol. 117, 977-983. https://doi.org/10.1046/j.0022-202x.2001.01484.x
  3. Dillon, S.R., Sprecher, C., Hammond, A., Bilsborough, J., Rosenfeld-Franklin, M., Presnell, S.R., Haugen, H.S., Maurer, M., Harder, B., Johnston, J., Bort, S., Mudri, S., Kuijper, J.L., Bukowski, T., Shea, P., Dong, D.L., Dasovich, M., Grant, F.J., Lockwood, L., Levin, S.D., LeCiel, C., Waggie, K., Day, H., Topouzis, S., Kramer, J., Kuestner, R., Chen, Z., Foster, D., Parrish-Novak, J. and Gross, J.A. (2004) Interleukin 31, a cytokine produced by activated T cells, induces dermatitis in mice. Nat Immunol. 5, 752-760.
  4. Friedmann, P.S. (2006) Contact sensitisation and allergic contact dermatitis: immunobiological mechanisms. Toxicol Lett. 162, 49-54. https://doi.org/10.1016/j.toxlet.2005.10.008
  5. Guo, T.L., Zhang, X.L., Leffel, E.K., Peachee, V.L., Karrow, N.A., Germolec, D.R. and White, K.L., Jr. (2002) Differential stimulation of IgE production, STAT activation and cytokine and CD86 expression by 2,4-dinitrochlorobenzene and trimellitic anhydride. J Appl Toxicol. 22, 397-403. https://doi.org/10.1002/jat.876
  6. Gustafsson, D., Sjoberg, O. and Foucard, T. (2000) Development of allergies and asthma in infants and young children with atopic dermatitis--a prospective follow-up to 7 years of age. Allergy. 55, 240-245. https://doi.org/10.1034/j.1398-9995.2000.00391.x
  7. Hamid, Q., Boguniewicz, M. and Leung, D.Y. (1994) Differential in situ cytokine gene expression in acute versus chronic atopic dermatitis. J Clin Invest. 94, 870-876. https://doi.org/10.1172/JCI117408
  8. Horsmanheimo, L., Harvima, I.T., Jarvikallio, A., Harvima, R.J., Naukkarinen, A. and Horsmanheimo, M. (1994) Mast cells are one major source of interleukin-4 in atopic dermatitis. Br J Dermatol. 131, 348-353. https://doi.org/10.1111/j.1365-2133.1994.tb08522.x
  9. Inoue, Y., Isobe, M., Shiohara, T., Goto, Y. and Hayashi, H. (2002) Protective and curative effects of topically applied CX- 659S, a novel diaminouracil derivative, on chronic picryl chloride-induced contact hypersensitivity responses. Br J Dermatol. 147, 675-682. https://doi.org/10.1046/j.1365-2133.2002.04917.x
  10. Jin, H., He, R., Oyoshi, M. and Geha, R.S. (2009) Animal models of atopic dermatitis. J Invest Dermatol. 129, 31-40. https://doi.org/10.1038/jid.2008.106
  11. Kang, J.S., Lee, K., Han, S.B., Ahn, J.M., Lee, H., Han, M.H., Yoon, Y.D., Yoon, W.K., Park, S.K. and Kim, H.M. (2006) Induction of atopic eczema/dermatitis syndrome-like skin lesions by repeated topical application of a crude extract of Dermatophagoides pteronyssinus in NC/Nga mice. Int Immunopharmacol. 6, 1616-1622. https://doi.org/10.1016/j.intimp.2006.06.011
  12. Kim, E.C., Lee, H.S., Kim, S.K., Choi, M.S., Lee, S., Han, J.B., An, H.J., Um, J.Y., Kim, H.M., Lee, N.Y., Bae, H. and Min, B.I. (2008) The bark of Betula platyphylla var. japonica inhibits the development of atopic dermatitis-like skin lesions in NC/Nga mice. J Ethnopharmacol. 116, 270-278. https://doi.org/10.1016/j.jep.2007.11.042
  13. Kimber, I., Basketter, D.A., Berthold, K., Butler, M., Garrigue, J.L., Lea, L., Newsome, C., Roggeband, R., Steiling, W., Stropp, G., Waterman, S. and Wiemann, C. (2001) Skin sensitization testing in potency and risk assessment. Toxicol Sci. 59, 198- 208. https://doi.org/10.1093/toxsci/59.2.198
  14. Kitagaki, H., Fujisawa, S., Watanabe, K., Hayakawa, K. and Shiohara, T. (1995) Immediate-type hypersensitivity response followed by a late reaction is induced by repeated epicutaneous application of contact sensitizing agents in mice. J Invest Dermatol. 105, 749-755. https://doi.org/10.1111/1523-1747.ep12325538
  15. Kitagaki, H., Ono, N., Hayakawa, K., Kitazawa, T., Watanabe, K. and Shiohara, T. (1997) Repeated elicitation of contact hypersensitivity induces a shift in cutaneous cytokine milieu from a T helper cell type 1 to a T helper cell type 2 profile. J Immunol. 159, 2484-2491.
  16. Lee, H.S., Kim, S.K., Han, J.B., Choi, H.M., Park, J.H., Kim, E.C., Choi, M.S., An, H.J., Um, J.Y., Kim, H.M. and Min, B.I. (2006) Inhibitory effects of Rumex japonicus Houtt. on the development of atopic dermatitis-like skin lesions in NC/Nga mice. Br J Dermatol. 155, 33-38. https://doi.org/10.1111/j.1365-2133.2006.07303.x
  17. Leung, D.Y., Boguniewicz, M., Howell, M.D., Nomura, I. and Hamid, Q.A. (2004) New insights into atopic dermatitis. J Clin Invest. 113, 651-657.
  18. Man, M.Q., Hatano, Y., Lee, S.H., Man, M., Chang, S., Feingold, K.R., Leung, D.Y., Holleran, W., Uchida, Y. and Elias, P.M. (2008) Characterization of a hapten-induced, murine model with multiple features of atopic dermatitis: structural, immunologic, and biochemical changes following single versus multiple oxazolone challenges. J Invest Dermatol. 128, 79-86. https://doi.org/10.1038/sj.jid.5701011
  19. Marsella, R. and Olivry, T. (2003) Animal models of atopic dermatitis. Clin Dermatol. 21, 122-133. https://doi.org/10.1016/S0738-081X(02)00369-3
  20. Matsuda, H., Watanabe, N., Geba, G.P., Sperl, J., Tsudzuki, M., Hiroi, J., Matsumoto, M., Ushio, H., Saito, S., Askenase, P.W. and Ra, C. (1997) Development of atopic dermatitis-like skin lesion with IgE hyperproduction in NC/Nga mice. Int Immunol. 9, 461-466. https://doi.org/10.1093/intimm/9.3.461
  21. Navi, D., Saegusa, J. and Liu, F.T. (2007) Mast cells and immunological skin diseases. Clin Rev Allergy Immunol. 33, 144-155. https://doi.org/10.1007/s12016-007-0029-4
  22. Nomura, I., Goleva, E., Howell, M.D., Hamid, Q.A., Ong, P.Y., Hall, C.F., Darst, M.A., Gao, B., Boguniewicz, M., Travers, J.B. and Leung, D.Y. (2003) Cytokine milieu of atopic dermatitis, as compared to psoriasis, skin prevents induction of innate immune response genes. J Immunol. 171, 3262-3269.
  23. Novak, N. (2009) New insights into the mechanism and management of allergic diseases: atopic dermatitis. Allergy. 64, 265-275. https://doi.org/10.1111/j.1398-9995.2008.01922.x
  24. Novak, N. and Bieber, T. (2005) The role of dendritic cell subtypes in the pathophysiology of atopic dermatitis. J Am Acad Dermatol. 53, S171-176. https://doi.org/10.1016/j.jaad.2005.04.060
  25. Opal, S.M. and DePalo, V.A. (2000) Anti-inflammatory cytokines. Chest. 117, 1162-1172. https://doi.org/10.1378/chest.117.4.1162
  26. Shiohara, T., Hayakawa, J. and Mizukawa, Y. (2004) Animal models for atopic dermatitis: are they relevant to human disease? J Dermatol Sci. 36, 1-9. https://doi.org/10.1016/j.jdermsci.2004.02.013
  27. Spergel, J.M., Mizoguchi, E., Brewer, J.P., Martin, T.R., Bhan, A.K. and Geha, R.S. (1998) Epicutaneous sensitization with protein antigen induces localized allergic dermatitis and hyperresponsiveness to methacholine after single exposure to aerosolized antigen in mice. J Clin Invest. 101, 1614-1622. https://doi.org/10.1172/JCI1647
  28. Sugiura, K., Shamoto, M., Sakamoto, N., Shinzato, M., Osada, A., Sugiura, M., Hayakawa, R. and Kato, Y. (2003) It is true that, when Langerhans cells migrate from the skin to the lymph node, they are transported via lymph vessels. Dermatology. 206, 222-224. https://doi.org/10.1159/000068902
  29. Sunada, Y., Nakamura, S. and Kamei, C. (2008) Effect of Lactobacillus acidophilus strain L-55 on the development of atopic dermatitis-like skin lesions in NC/Nga mice. Int Immunopharmacol. 8, 1761-1766. https://doi.org/10.1016/j.intimp.2008.08.011
  30. Tanaka, T., Tsutsui, H., Yoshimoto, T., Kotani, M., Matsumoto, M., Fujita, A., Wang, W., Higa, S., Koshimoto, T., Nakanishi, K. and Suemura, M. (2001) Interleukin-18 is elevated in the sera from patients with atopic dermatitis and from atopic dermatitis model mice, NC/Nga. Int Arch Allergy Immunol. 125, 236-240. https://doi.org/10.1159/000053821
  31. Taniguchi, Y., Kohno, K., Inoue, S., Koya-Miyata, S., Okamoto, I., Arai, N., Iwaki, K., Ikeda, M. and Kurimoto, M. (2003) Oral administration of royal jelly inhibits the development of atopic dermatitis-like skin lesions in NC/Nga mice. Int Immunopharmacol. 3, 1313-1324. https://doi.org/10.1016/S1567-5769(03)00132-2
  32. Theiner, G., Gessner, A. and Lutz, M.B. (2006) The mast cell mediator PGD2 suppresses IL-12 release by dendritic cells leading to Th2 polarized immune responses in vivo. Immunobiology. 211, 463-472. https://doi.org/10.1016/j.imbio.2006.05.020
  33. Wollenberg, A. and Klein, E. (2007) Current aspects of innate and adaptive immunity in atopic dermatitis. Clin Rev Allergy Immunol. 33, 35-44. https://doi.org/10.1007/s12016-007-0032-9
  34. Yamanaka, K., Tanaka, M., Tsutsui, H., Kupper, T.S., Asahi, K., Okamura, H., Nakanishi, K., Suzuki, M., Kayagaki, N., Black, R.A., Miller, D.K., Nakashima, K., Shimizu, M. and Mizutani, H. (2000) Skin-specific caspase-1-transgenic mice show cutaneous apoptosis and pre-endotoxin shock condition with a high serum level of IL-18. J Immunol. 165, 997-1003.
  35. Yatsuzuka, R., Inoue, T., Jiang, S., Nakano, Y. and Kamei, C. (2007) Development of new atopic dermatitis models characterized by not only itching but also inflammatory skin in mice. Eur J Pharmacol. 565, 225-231. https://doi.org/10.1016/j.ejphar.2007.02.062