Skip to main content
SpringerLink
Log in

Effects of topical application of a recombinant staphylococcal enterotoxin A on DNCB and dust mite extract-induced atopic dermatitis-like lesions in a murine model

  • Investigative Report
  • Published:
European Journal of Dermatology Aims and scope

Abstract

Background

Atopic dermatitis (AD) is a chronic inflammatory skin disease with biphasic T cell-mediated abnormalities. Staphylococcal superantigens contribute to the exacerbation of inflammation in AD. The underlying immunopathological mechanisms are not fully understood.

Objective

To determine whether epicutaneous application of recombinant staphylococcal enterotoxin A (rSEA) would exacerbate AD-like allergic inflammation induced by 2, 4-dinitrochlorobenzene (DNCB) and house dust mite extract (Dermatophagoides farinae extract, DFE) in a murine model.

Materials and Methods

We first established an AD-like model using BALB/c mice exposed to DNCB/DFE on the ear. Next, Staphylococcus (S.) aureus or rSEA were topically applied to the mice. We evaluated the clinical and histopathological features of the animals. Serum immunoglobulin levels were also measured. In addition, real-time PCR analysis of cytokines produced by T cell subsets in the earswas conducted.

Results

Mice treated with S. aureus and rSEA had more severe clinical symptoms, including increased mean dermatitis scores and ear thickness, compared to animals with only AD-like lesions. Total IgE, IgG2a and serum histamine levels were increased in all groups except the normal control group. The S. Aureus- and rSEA-treated groups showed increased levels of cytokines such as IL-4, IL-13, INF-γ, IL-17, and IL-18. In particular, increased cytokine expressionwas more conspicuous in the rSEA-treated group than in mice exposed to S. aureus.

Conclusion

The results of this study showed that topical exposure to rSEA as well as SEA-producing S. aureus aggravate atopic skin inflammation. This may be associated with the induction of a mixed Th1/Th2 type dermatitis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Pastar Z, Lipozencic J, Ljubojevic S. Etiopathogenesis of atopic dermatitis-an overview. Acta Dermatovenerol Croat 2005; 13: 54–62.

    PubMed  Google Scholar 

  2. Yamamoto M, Haruna T, Yasui K, et al. A novel atopic dermatitis model induced by topical application with dermatophagoides farinae extract in NC/Nga mice. Allergol Int 2007; 56: 139–148.

    Article  PubMed  Google Scholar 

  3. Lubbe J. Secondary infections in patients with atopic dermatitis. Am J Clin Dermatol 2003; 4: 641–654.

    Article  PubMed  Google Scholar 

  4. Leyden JJ, Marples RR, Kligman AM. Staphylococcus aureus in the lesions of atopic dermatitis. Br J Dermatol 1974; 90: 525–530.

    Article  CAS  PubMed  Google Scholar 

  5. Ring J, Abeck D, Neuber K. Atopic eczema: role of microorganisms on the skin surface. Allergy 1992; 47: 265–269.

    Article  CAS  PubMed  Google Scholar 

  6. Lin YT, Wang CT, Chiang BL. Role of bacterial pathogens in atopic dermatitis. Clin Rev Allergy Immunol 2007; 33: 167–177.

    Article  CAS  PubMed  Google Scholar 

  7. Guzik TJ, Bzowska M, Kasprowicz A, et al. Persistent skin colonization with Staphylococcus aureus in atopic dermatitis: relationship to clinical and immunological parameters. Clin Exp Allergy 2005; 35: 448–455.

    Article  CAS  PubMed  Google Scholar 

  8. Nilsson EJ, Henning CG, Magnusson J. Topical corticosteroids and Staphylococcus aureus in atopic dermatitis. J Am Acad Dermatol 1992; 27: 29–34.

    Article  CAS  PubMed  Google Scholar 

  9. Proft T, Fraser JD. Bacterial superantigens. Clin Exp Immunol 2003; 133: 299–306.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Jung HJ, Jun JH, Cha HW, et al. Effect of topical application of staphylococcus aureus in the DNCB and dust mite extract-induced murine model with atopic dermatitis-Like Lesions. Korean J Dermatol 2011; 49(Suppl. 2): 124.

    Google Scholar 

  11. Kwon HK, Lee CG, So JS, et al. Generation of regulatory dendritic cells and CD4+Foxp3+ T cells by probiotics administration suppresses immune disorders. Proc Natl Acad Sci USA 2010; 107: 2159–2164.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Choi EJ, Lee S, Hwang JS, et al. DA-9601 suppresses 2, 4-dinitrochlorobenzene and dust mite extract-induced atopic dermatitis-like skin lesions. Int Immunopharmacol 2011; 11: 1260–1264.

    Article  CAS  PubMed  Google Scholar 

  13. Liu F, Lin LR, Zhang HL, et al. Laboratorial characteristics of patients with diarrhea suffering from egg white allergy. Allergol Immunopathol (Madr) 2013 Jul 11 [Epub ahead of print].

    Google Scholar 

  14. Shore PA, Burkhalter A, Cohn VH Jr.. A method for the fluorometric assay of histamine in tissues. J Pharmacol Exp Ther 1959; 127: 182–186.

    CAS  PubMed  Google Scholar 

  15. Kim SH, Lee S, Suk K, et al. Discoidin domain receptor 1 mediates collagen-induced nitric oxide production in J774A.1 murine macrophages. Free Radic Biol Med 2007; 42: 343–352.

    Article  PubMed  Google Scholar 

  16. Karrer S, Bosserhoff AK, Weiderer P, Landthaler M, Szeimies RM. Influence of 5-aminolevulinic acid and red light on collagen metabolism of human dermal fibroblasts. J Invest Dermatol 2003; 120: 325–331.

    Article  CAS  PubMed  Google Scholar 

  17. Cardona ID, Cho SH, Leung DY. Role of bacterial superantigens in atopic dermatitis: implications for future therapeutic strategies. Am J Clin Dermatol 2006; 7: 273–279.

    Article  PubMed  Google Scholar 

  18. Kim DW, Park JY, Park KD, et al. Are there predominant strains and toxins of Staphylococcus aureus in atopic dermatitis patients? Genotypic characterization and toxin determination of S. aureus isolated in adolescent and adult patients with atopic dermatitis. J Dermatol 2009; 36: 75–81.

    Article  CAS  PubMed  Google Scholar 

  19. Tomi NS, Kränke B, Aberer E. Staphylococcal toxins in patients with psoriasis, atopic dermatitis, and erythroderma, and in healthy control subjects. J Am Acad Dermatol 2005; 53: 67–72.

    Article  PubMed  Google Scholar 

  20. Bunikowski R, Mielke ME, Skarabis H, et al. Evidence for a disease-promoting effect of Staphylococcus aureus-derived exotoxins in atopic dermatitis. J Allergy Clin Immunol 2000; 105: 814–819.

    Article  CAS  PubMed  Google Scholar 

  21. Yagi S, Wakaki N, Ikeda N, et al. Presence of staphylococcal exfoliative toxin A in sera of patients with atopic dermatitis. Clin Exp Allergy 2004; 34: 984–993.

    Article  CAS  PubMed  Google Scholar 

  22. Kim BS, Kim JY, Lim HJ, et al. Colonizing features of Staphylococcus aureus in early childhood atopic dermatitis and in mothers: a cross-sectional comparative study done at four kindergartens in Daegu, South Korea. Ann Allergy Asthma Immunol 2011; 106: 323–329.

    Article  PubMed  Google Scholar 

  23. Williams RE, Gibson AG, Aitchison TC, Lever R, Mackie RM. Assessment of a contact-plate sampling technique and subsequent quantitative bacterial studies in atopic dermatitis. Br J Dermatol 1990; 123: 493–501.

    Article  CAS  PubMed  Google Scholar 

  24. Gong JQ, Lin L, Lin T, et al. Skin colonization by Staphylococcus aureus in patients with eczema and atopic dermatitis and relevant combined topical therapy: a double-blind multicentre randomized controlled trial. Br J Dermatol 2006; 155: 680–687.

    Article  CAS  PubMed  Google Scholar 

  25. Guttman-Yassky E, Nograles KE, Krueger JG. Contrasting pathogenesis of atopic dermatitis and psoriasis-part II: immune cell subsets and therapeutic concepts. J Allergy Clin Immunol. 2011; 127: 1420–1432.

    Article  CAS  PubMed  Google Scholar 

  26. Liu FT, Goodarzi H, Chen HY. IgE, mast cells, and eosinophils in atopic dermatitis. Clin Rev Allergy Immunol. 2011; 41: 298–310.

    Article  CAS  PubMed  Google Scholar 

  27. Savinko T, Lauerma A, Lehtimaki S, et al. Topical superantigen exposure induces epidermal accumulation of CD8+ T cells, a mixed Th1/Th2-type dermatitis and vigorous production of IgE antibodies in the murine model of atopic dermatitis. J Immunol 2005; 175: 8320–8326.

    Article  CAS  PubMed  Google Scholar 

  28. Terada M, Tsutsui H, Imai Y, et al. Contribution of IL-18 to atopic-dermatitis-like skin inflammation induced by Staphylococcus aureus product in mice. Proc Natl Acad Sci USA 2006; 103: 8816–8821.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Hong SW, Kim MR, Lee EY, et al. Extracellular vesicles derived from Staphylococcus aureus induce atopic dermatitis-like skin inflammation. Allergy 2011; 66: 351–359.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Aral M, Arican O, Gul M, et al. The relationship between serum levels of total IgE, IL-18, IL-12, IFN-gamma and disease severity in children with atopic dermatitis. Mediators Inflamm 2006; 2006: 73098.

    PubMed Central  PubMed  Google Scholar 

  31. Bunikowski R, Mielke M, Skarabis H, et al. Prevalence and role of serum IgE antibodies to the Staphylococcus aureus-derived superantigens SEA and SEB in children with atopic dermatitis. J Allergy Clin Immunol 1999; 103: 119–124.

    Article  CAS  PubMed  Google Scholar 

  32. Ong PY, Patel M, Ferdman RM, Dunaway T, Church JA. Association of staphylococcal superantigen-specific immunoglobulin e with mild and moderate atopic dermatitis. J Pediatr 2008; 153: 803–806.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Kim MJ, Choung SY. Mixture of Polyphenols and Anthocyanins from Vaccinium uliginosum L. Alleviates DNCB-Induced Atopic Dermatitis in NC/Nga Mice. Evid Based Complement Alternat Med 2012 Oct 23. doi: 10.1155/2012/461989 [Epub ahead of print].

    Google Scholar 

  34. Matsushima Y, Kikkawa Y, Takada T, et al. An atopic dermatitislike skin disease with hyper-IgE-emia develops in mice carrying a spontaneous recessive point mutation in the Traf3ip2 (Act1/CIKS) gene. J Immunol 2010; 185: 2340–2349.

    Article  CAS  PubMed  Google Scholar 

  35. Koga C, Kabashima K, Shiraishi N, Kobayashi M, Tokura Y. Possible pathogenic role of Th17 cells for atopic dermatitis. J Invest Dermatol 2008; 128: 2625–2630.

    Article  CAS  PubMed  Google Scholar 

  36. Orfali RL, Sato MN, Takaoka R, et al. Atopic dermatitis in adults: evaluation of peripheral blood mononuclear cells proliferation response to Staphylococcus aureus enterotoxins A and B and analysis of interleukin-18 secretion. Exp Dermatol 2009; 18: 628–633.

    Article  CAS  PubMed  Google Scholar 

  37. Inoue Y, Aihara M, Kirino M, et al. Interleukin-18 is elevated in the horny layer in patients with atopic dermatitis and is associated with Staphylococcus aureus colonization. Br J Dermatol 2011; 164: 560–567.

    CAS  PubMed  Google Scholar 

  38. Raap U, Weißmantel S, Gehring M, Eisenberg AM, Kapp A, Fölster-Holst R. IL-31 significantly correlates with disease activity and Th2 cytokine levels in children with atopic dermatitis. Pediatr Allergy Immunol 2012; 23: 285–288

    Article  PubMed  Google Scholar 

  39. Sonkoly E, Muller A, Lauerma AI, et al. IL-31: a new link between T cells and pruritus in atopic skin inflammation. J Allergy Clin Immunol 2006; 117: 411–417.

    Article  CAS  PubMed  Google Scholar 

  40. Akdis M, Trautmann A, Klunker S, Blaser K, Akdis CA. Cytokine and anti-cytokine therapies for psoriasis and atopic dermatitis. Acta Odontol Scand 2001; 59: 178–182.

    Article  CAS  PubMed  Google Scholar 

  41. Kasraie S, Niebuhr M, Werfel T. Interleukin (IL)-31 induces proinflammatory cytokines in human monocytes and macrophages following stimulation with staphylococcal exotoxins. Allergy 2010; 65: 712–721.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Dermatology, Pusan National University Hospital, Busan, Republic of Korea

    Byung Soo Kim

  2. Biomedical Research Institute, Pusan National University Hospital, Busan, Republic of Korea

    Byung Soo Kim

  3. Department of Pharmacology, Kyungpook National University School of Medicine, 200 Dongduk-ro, Jung-gu, Daegu, 700-721, Republic of Korea

    Jin Kyeong Choi & Sang-Hyun Kim

  4. Department of Dermatology, Kyungpook National University School of Medicine, 200 Dongduk-ro, Jung-gu, Daegu, 700-721, Republic of Korea

    Han Jin Jung, Kyung Hea Park, Yong Hyun Jang, Weon Ju Lee, Seok-Jong Lee & Do Won Kim

  5. Kyungpook National University School of Medicine, 200 Dongduk-ro, Jung-gu, Daegu, 700-721, Republic of Korea

    Hee Young Kang & Jung Min Kim

  6. Yeil Skin Clinic, Daegu, Republic of Korea

    Hyun Jung Lim

Authors
  1. Byung Soo Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jin Kyeong Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Han Jin Jung
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kyung Hea Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yong Hyun Jang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Weon Ju Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Seok-Jong Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Sang-Hyun Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Hee Young Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jung Min Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Hyun Jung Lim
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Do Won Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Do Won Kim.

Additional information

These authors contributed equally to this work.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kim, B.S., Choi, J.K., Jung, H.J. et al. Effects of topical application of a recombinant staphylococcal enterotoxin A on DNCB and dust mite extract-induced atopic dermatitis-like lesions in a murine model. Eur J Dermatol 24, 186–193 (2014). https://doi.org/10.1684/ejd.2014.2302

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1684/ejd.2014.2302

Key words

Search

Navigation