Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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Molecular Mechanism of Atopic Dermatitis Induction Following Sensitization and Challenge with 2,4-Dinitrochlorobenzene in Mouse Skin Tissue

  • Kim, JiYoun (Department of Occupational Health, Catholic University of Daegu) ;
  • Lee, JaeHee (Department of Occupational Health, Catholic University of Daegu) ;
  • Shin, SoJung (Department of Occupational Health, Catholic University of Daegu) ;
  • Cho, AhRang (Department of Occupational Health, Catholic University of Daegu) ;
  • Heo, Yong (Department of Occupational Health, Catholic University of Daegu)
  • Received : 2017.09.19
  • Accepted : 2017.10.20
  • Published : 2018.01.15
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Abstract

Laboratory animal models have been developed to investigate preventive or therapeutic effect of medicinal products, or occurrence or progression mechanism of atopic dermatitis (AD), a pruritic and persistent inflammatory skin disease. The murine model with immunologic phenomena resembling human AD was introduced, which demonstrated skewedness toward predominance of type-2 helper T cell reactivity and pathophysiological changes similar as human AD following 2,4-dinitrochlorobenzene (DNCB) sensitization and challenge. Molecular mechanism on the DNCB-mediated AD was further evaluated. Skin tissues were collected from mice treated with DNCB, and each tissue was equally divided into two sections; one for protein and the other for mRNA analysis. Expression of filaggrin, an important protein for keratinocyte integrity, was evaluated through SDS-PAGE. Level of mRNA expression for cytokines was determined through semi-quantitative reverse transcriptase polymerase chain reaction. Expression of filaggrin protein was significantly enhanced in the mice treated with DNCB compared with the vehicle (acetone : olive oil = 4 : 1 mixture) treatment group or the normal group without any treatment. Level of tumor necrosis factor-alpha and interleukin-18 mRNA expression, cytokines involved in activity of type-1 helper T ($T_H1$) cell, was significantly downregulated in the AD group compared with other control groups. These results suggest that suppression of $T_H1$ cell-mediated immune response could be reflected into the skin tissue of mice treated with DNCB for AD induction, and disturbance of keratinocyte integrity might evoke a compensatory mechanism.

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References

  1. Weidinger, S. and Novak, N. (2016) Atopic dermatitis. Lancet, 387, 1109-1122. https://doi.org/10.1016/S0140-6736(15)00149-X
  2. Deckers, I.A., McLean, S., Linssen, S., Mommers, M., van Schayck, C.P. and Sheikh, A. (2012) Investigating international time trends in the incidence and prevalence of atopic eczema 1990-2010: a systematic review of epidemiological studies. PLoS ONE, 7, e39803. https://doi.org/10.1371/journal.pone.0039803
  3. Egawa, G. and Weninger, W. (2015) Pathogenesis of atopic dermatitis: a short review. Cogent Biol., 1, 1103459.
  4. Hensel, P., Santoro, D., Favrot, C., Hill, P. and Griffin, C. (2015) Canine atopic dermatitis: detailed guidelines for diagnosis and allergen identification. BMC Vet. Res., 11, 196.
  5. Matsumoto, M., Ra, C., Kawamoto, K., Sato, H., Itakura, A., Sawada, J., Ushio, H., Suto, H., Mitsuishi, K., Hikasa, Y. and Matsuda, H. (1999) IgE hyperproduction through enhanced tyrosine phosphorylation of Janus kinase 3 in NC/Nga mice, a model for human atopic dermatitis. J. Immunol., 162, 1056-1063.
  6. Konishi, H., Tsutsui, H., Murakami, T., Yumikura-Futatsugi, S., Yamanaka, K., Tanaka, M., Iwakura, Y., Suzuki, N., Takeda, K., Akira, S., Nakanishi, K. and Mizutani, H. (2002) IL-18 contributes to the spontaneous development of atopic dermatitis-like inflammatory skin lesion independently of IgE/stat6 under specific pathogen-free conditions. PNAS, 99, 11340-11345. https://doi.org/10.1073/pnas.152337799
  7. Lee, G.R. and Flavell, R.A. (2004) Transgenic mice which overproduces Th2 cytokines develop spontaneous atopic dermatitis and asthma. Int. Immunol., 16, 1150-1160.
  8. 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
  9. Yoshioka, T., Hikita, I., Matsutani, T., Yoshida, R., Asakawa, M., Toyosaki-Maeda, T., Hirasawa, T., Suzuki, R., Arimura, A. and Horikawa, T. (2003) DS-Nh as an experimental model of atopic dermatitis induced by Staphylococcus aureus producing staphylococcal enterotoxin. Cell. Immunol., 108, 562-569.
  10. Kim, S.-N., Kim, Y.-C., Kim, H.-A. and Heo, Y. (2011) A potential mechanism of 2,4-dinitrochlorobenzene-mediated immune alterations resembling human atopic dermatitis in mice. Quant. Bio-Sci., 30, 85-90.
  11. Lee, S.H., Baek, S.J., Kim, H.A. and Heo, Y. (2006) 2,4-Dinitrochlorobenzene-induced atopic dermatitis like immune alteration in mice. Toxicol. Res., 22, 357-364.
  12. Cook, P.C., Jones, L.H., Jenkins, S.J., Wynn, T.A., Allen, J.E. and MacDonald, A.S. (2012) Alternatively activated dendritic cells regulate $CD4^+$ T-cell polarization in vitro and in vivo. PNAS, 109, 9977-9982.
  13. Lee, S.-H., Heo, Y. and Kim, Y.-C. (2010) Effect of German chamomile oil application on alleviating atopic dermatitis-like immune alterations in mice. J. Vet. Sci., 11, 35-41. https://doi.org/10.4142/jvs.2010.11.1.35
  14. Wu, Z., Hansmann, B., Meyer-Hoffert, U., Glaser, R. and Schroder, J.-M. (2009) Molecular identification and expression analysis of filaggarin-2, a member of the S100 fusedtype protein family. PLoS ONE, 4, e5227. https://doi.org/10.1371/journal.pone.0005227
  15. Heo, Y., Mondal, T.K., Gao, D., Kasten-Jolly, J., Kishikawa, H. and Lawrence, D.A. (2007) Posttranscriptional inhibition of interferon-gamma production by lead. Toxicol. Sci., 96, 92-100.
  16. Chen, L., Segal, D.M. and Mash, D.C. (1999) Semi-quantitative reverse-transcriptase polymerase chain reaction: an approach for the measurement of target gene expression in human brain. Brain Res. Prot., 4, 132-139.
  17. Cabanillas, B. and Novak, N. (2016) Atopic dermatitis and filaggrin. Curr. Opi. Immunol., 42, 1-8. https://doi.org/10.1016/j.coi.2016.05.002
  18. Matsunaga, M.C. and Yamauchi, P.S. (2016) IL-4 and IL-13 inhibition in atopic dermatitis. J. Drugs Dermatol., 15, 925-929.
  19. Dinarello, C.A., Novick, D., Kim, S. and Kaplanski, G. (2013) Interleukin-18 and IL-18 binding protein. Front. Immunol., 4, 289.
  20. Bashir, M.M., Sharma, M.R. and Werth, V.P. (2009) TNF-alpha production in skin. Arch. Dermatol. Res., 30, 87-91.
  21. Brown, S.J. and Irwin McLean, W.H. (2012) One remarkable molecule: Filaggrin. J. Invest. Dermatol., 132, 751-762. https://doi.org/10.1038/jid.2011.393
  22. Thyssen, J.P. and Kezic, S. (2014) Causes of epidermal filaggrin reduction and their role in the pathogenesis of atopic dermatitis. J. Allergy Clin. Immunol., 134, 792-799. https://doi.org/10.1016/j.jaci.2014.06.014
  23. Sandilands, A., Sutherland, C., Irvine, A.D. and Irwin McLean, W.H. (2009) Filaggrin in the frontline: role in skin barrier function and disease. J. Cell Sci., 122, 1285-1294. https://doi.org/10.1242/jcs.033969
  24. Visser, M.J., Verberk, M.M., Campbell, L.E., Irwin Mclean, W.H., Calkoen, F., Bakker, J.G., van Dijk, F.J.H., Bos, J.D. and Kezic, S. (2013) Filaggrin los-of-function mutations and atopic dermatitis as risk factors for hand eczema in apprentice nurses: part II of a prospective cohort study. Contact Derm., 70, 139-150.
  25. Furue, M., Tsuji, G., Mitoma, C., Nakahara, T., Chiba, T., Morino-Koga, S. and Uchi, H. (2015) Gene regulation of filaggrin and other skin barrier proteins via aryl hydrocarbon receptor. J. Dermatol. Sci., 80, 83-88.
  26. Ye, Y.-M., Km, B.-Y., Shin, Y.-S., Park, H.-S. and Leung, D.Y.M. (2014) Increased epidermal filaggrin in chronic idiopathic urticarial is associated with severity of urticaria. Ann. Allergy Asthma Immunol., 112, 533-538.
  27. Yoshimoto, T., Takeda, K., Tanaka, T., Ohkusu, K., Kashiwamura, S., Okamura, H., Akira, S. and Nakanishi, K. (1998) IL-12 up-regulates IL-18 receptor expression on T cells, Th1 cells, and B cells: synergism with IL-18 for IFN-g production. J. Immunol., 161, 3400-3407.
  28. Wang, A. and Landen, N.X. (2015) New insights into T cells and their signature cytokines in atopic dermatitis. IUBMB, 67, 601-610. https://doi.org/10.1002/iub.1405
  29. Lee, J., Cho, D. and Park, H. (2015) IL-18 and cutaneous inflammatory diseases. Int. J. Mol.Sci., 16, 29357-29369. https://doi.org/10.3390/ijms161226172
  30. Stoll, S., Muller, G., Kurimoto, M., Saloga, J., Tanimoto, T., Yamauchi, H., Okamura, H., Knop, J. and Enk, A.H. (1997) Production of IL-18 (IFN-gamma-inducing factor) messenger RNA and functional protein by murine keratinocytes. J. Immunol., 159, 298-302.
  31. Gosmann, C., Frazer, I.H., Mattarollo, S.R. and Blumenthal, A. (2014) IL-18, but not IL-12, induces production of IFN-g in the immunosuppressive environment of HPV16 E7 transgenic hyperplastic skin. J. Invest. Dermatol., 134, 2562-2569. https://doi.org/10.1038/jid.2014.201
  32. Kampfer, H., Kalina, U., Mühl, H., Pfeilschofter, J. and Frank, S. (1999) Counterregulation of interleukin-18 mRNA and protein expression during cutaneous wound repair in mice. J. Invets. Dermatol., 113, 369-374. https://doi.org/10.1046/j.1523-1747.1999.00704.x
  33. Heo, Y., Zhang, Y., Gao, D., Miller, V.M. and Lawrence, D.A. (2011) Aberrant immune responses in a mouse with behavioral disorders. PLoS ONE, 6, e20912. https://doi.org/10.1371/journal.pone.0020912
  34. Ravi, G., Heo, Y., Lim, G.-D., Song, E.-S., Roque, K., Lee, J.-H., Kim, Y.-G., Cho, A.-R., Shin, S.-J., Kim, C.-Y., Bang, G.-H., Bahng, J.-Y. and Kim, H.-A. (2017) Altered immune responses in broiler chicken husbandry workers and their association with endotoxin exposure. Ind. Health, doi: 10.2486/indhealth.2017-0049 [Epub ahead of print].
  35. Dalessandri, T., Crawford, G., Hayes, M., Seoane, R.C. and Strid, J. (2016) IL-13 from intraepithelial lymphocytes regulates tissue homeostasis and protect against carcinogenesis in the skin. Nat. Commun., 7, 12080. https://doi.org/10.1038/ncomms12080
  36. Oh, M.-H., Oh, S.-Y., Lu, J., Lou, H., Myers, A.C., Zhu, Z. and Zheng, T. (2013) TRPA1-dependent pruritis in IL-13-induced chronic atopic dermatitis. J. Immunol., 191, 5371-5382. https://doi.org/10.4049/jimmunol.1300300

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