Skip to main content

Advertisement

Springer Nature Link
Log in

Improvement of atopic dermatitis-like skin lesions by IL-4 inhibition of P14 protein isolated from Lactobacillus casei in NC/Nga mice

  • Biotechnologically relevant enzymes and proteins
  • Published:
Applied Microbiology and Biotechnology Aims and scope Submit manuscript

Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin disease, with a complex etiology encompassing immunologic responses. AD is frequently associated with elevated serum immunoglobulin (Ig) E levels and is exacerbated by a variety of environmental factors, which contribute to its pathogenesis. However, the etiology of AD remains unknown. Recently, reports have documented the role of lactic acid bacteria (LAB) in the treatment and prevention of AD in humans and mice. The LAB, Lactobacillus casei (LC), is frequently used in the treatment of AD. To identify the active component of LC, we screened fractions obtained from the ion exchange chromatography of LC extracts. Using this approach, we identified the candidate protein, P14. We examined whether the P14 protein has anti-atopic properties, using both in vitro and in vivo models. Our results showed that the P14 protein selectively downregulated serum IgE and interleukin-4 cytokine levels, as well as the AD index and scratching score in AD-like NC/Nga mice. In addition, histological examination was also effective in mice. These results suggest that the P14 protein has potential therapeutic effects and that it may also serve as an effective immunomodulatory agent for treating patients with AD.

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

Access this article

Log in via an institution

Subscribe and save

Springer+
from $39.99 /Month
  • Starting from 10 chapters or articles per month
  • Access and download chapters and articles from more than 300k books and 2,500 journals
  • Cancel anytime
View plans

Buy Now

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Explore related subjects

Discover the latest articles, books and news in related subjects, suggested using machine learning.

References

  • Abbas AK, Murphy KM, Sher A (1996) Functional diversity of helper T lymphocytes. Nature 383:787–793. doi:10.1038/383787a0

    Article  CAS  PubMed  Google Scholar 

  • Ahmed I, Nasreen S (2007) Frequency of raised serum IgE level in childhood atopic dermatitis. J Pak Med Assoc 57:431–434

    PubMed  Google Scholar 

  • Chan LS, Robinson N, 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 Investig Dermatol 117:977–983. doi:10.1046/j.0022-202x.2001.01484.x

    Article  CAS  PubMed  Google Scholar 

  • Chapat L, Chemin K, Dubois B, Bourdet-Sicard R, Kaiserlian D (2004) Lactobacillus casei reduces CD8+ T cell-mediated skin inflammation. Eur J Immunol 34:2520–2528. doi:10.1002/eji.200425139

    Article  CAS  PubMed  Google Scholar 

  • Donsky H, Clarke D (2007) Relieva, a Mahonia aquifolium extract for the treatment of adult patients with atopic dermatitis. Am J Ther 14:442–446. doi:10.1097/MJT.0b013e31814002c1

    Article  PubMed  Google Scholar 

  • Fujiwara D, Inoue S, Wakabayashi H, Fujii T (2004) The anti-allergic effects of lactic acid bacteria are strain dependent and mediated by effects on both Th1/Th2 cytokine expression and balance. Int Arch Allergy Immunol 135:205–215. doi:10.1159/000081305

    Article  CAS  PubMed  Google Scholar 

  • Gupta AK, Chow M (2003) Pimecrolimus: a review. J Eur Acad Dermatol Venereol 17:493–503

    Article  CAS  PubMed  Google Scholar 

  • Hengge UR, Ruzicka T, Schwartz RA, Cork MJ (2006) Adverse effects of topical glucocorticosteroids. J Am Acad Dermatol 54:1–15. doi:10.1016/j.jaad.2005.01.010, quiz 16-18

    Article  PubMed  Google Scholar 

  • Jeong MS, Choi SE, Kim JY, Kim JS, Kim EJ, Park KH, Lee do I, Joo SS, Lee CS, Bang H, Lee MK, Choi YW, Li KS, Moon NJ, Lee MW, Seo SJ (2010) Atopic dermatitis-like skin lesions reduced by topical application and intraperitoneal injection of Hirsutenone in NC/Nga mice. Clin Dev Immunol 2010:618517. doi:10.1155/2010/618517

    Article  PubMed Central  PubMed  Google Scholar 

  • Kalliomaki M, Isolauri E (2003) Role of intestinal flora in the development of allergy. Curr Opin Allergy Clin Immunol 3:15–20. doi:10.1097/01.all.0000053262.39029.a1

    Article  CAS  PubMed  Google Scholar 

  • Kim MS, Hur YG, Kim WG, Park BW, Ahn KS, Kim JJ, Bae H (2011) Inhibitory effect of Platycodon grandiflorum on T(H)1 and T(H)2 immune responses in a murine model of 2,4-dinitrofluorobenzene-induced atopic dermatitis-like skin lesions. Ann Allergy Asthma Immunol 106:54–61. doi:10.1016/j.anai.2010.10.020

    Article  PubMed  Google Scholar 

  • Kim MS, Kim WG, Chung HS, Park BW, Ahn KS, Kim JJ, Bae H (2012) Improvement of atopic dermatitis-like skin lesions by Platycodon grandiflorum fermented by Lactobacillus plantarum in NC/Nga mice. Biol Pharm Bull 35:1222–1229

    Article  CAS  PubMed  Google Scholar 

  • Klewicka E, Cukrowska B, Libudzisz Z, Slizewska K, Motyl I (2011) Changes in gut microbiota in children with atopic dermatitis administered the bacteria Lactobacillus casei DN–114001. Pol J Microbiol 60:329–333

    Article  PubMed  Google Scholar 

  • Klovekorn W, Tepe A, Danesch U (2007) A randomized, double-blind, vehicle-controlled, half-side comparison with a herbal ointment containing Mahonia aquifolium, Viola tricolor and Centella asiatica for the treatment of mild-to-moderate atopic dermatitis. Int J Clin Pharmacol Ther 45:583–591

    Article  CAS  PubMed  Google Scholar 

  • Larsen N, Vogensen FK, Gobel R, Michaelsen KF, Abu Al-Soud W, Sorensen SJ, Hansen LH, Jakobsen M (2011) Predominant genera of fecal microbiota in children with atopic dermatitis are not altered by intake of probiotic bacteria Lactobacillus acidophilus NCFM and Bifidobacterium animalis subsp. lactis Bi-07. FEMS Microbiol Ecol 75:482–496. doi:10.1111/j.1574-6941.2010.01024.x

    Article  CAS  PubMed  Google Scholar 

  • Laske N, Niggemann B (2004) Does the severity of atopic dermatitis correlate with serum IgE levels? Pediatr Allergy Immunol 15:86–88

    Article  PubMed  Google Scholar 

  • Lee HS, Kim SK, Han JB, Choi HM, Park JH, Kim EC, Choi MS, An HJ, Um JY, Kim HM, Min BI (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. doi:10.1111/j.1365-2133.2006.07303.x

    Article  PubMed  Google Scholar 

  • Leung DY (1997) Atopic dermatitis: immunobiology and treatment with immune modulators. Clin Exp Immunol 107(Suppl 1):25–30

    CAS  PubMed  Google Scholar 

  • Leung DY, Bieber T (2003) Atopic dermatitis. Lancet 361:151–160. doi:10.1016/S0140-6736(03)12193-9

    Article  PubMed  Google Scholar 

  • Lyu J, Kim JA, Chung SK, Kim KS, Joo CK (2003) Alteration of cadherin in dexamethasone-induced cataract organ-cultured rat lens. Invest Ophthalmol Vis Sci 44:2034–2040

    Article  PubMed  Google Scholar 

  • Mainardi T, Kapoor S, Bielory L (2009) Complementary and alternative medicine: herbs, phytochemicals and vitamins and their immunologic effects. J Allergy Clin Immunol 123:283–294. doi:10.1016/j.jaci.2008.12.023, quiz 295-286

    Article  CAS  PubMed  Google Scholar 

  • Matsuda H, Watanabe N, Geba GP, Sperl J, Tsudzuki M, Hiroi J, Matsumoto M, Ushio H, Saito S, Askenase PW, Ra C (1997) Development of atopic dermatitis-like skin lesion with IgE hyperproduction in NC/Nga mice. Int Immunol 9:461–466

    Article  CAS  PubMed  Google Scholar 

  • Mercenier A, Pavan S, Pot B (2003) Probiotics as biotherapeutic agents: present knowledge and future prospects. Curr Pharm Des 9:175–191

    Article  CAS  PubMed  Google Scholar 

  • Morar N, Willis-Owen SA, Moffatt MF, Cookson WO (2006) The genetics of atopic dermatitis. J Allergy Clin Immunol 118:24–34. doi:10.1016/j.jaci.2006.03.037, quiz 35-26

    Article  CAS  PubMed  Google Scholar 

  • Ogawa T, Hashikawa S, Asai Y, Sakamoto H, Yasuda K, Makimura Y (2006) A new synbiotic, Lactobacillus casei subsp. casei together with dextran, reduces murine and human allergic reaction. FEMS Immunol Med Microbiol 46:400–409. doi:10.1111/j.1574-695X.2006.00046.x

    Article  CAS  PubMed  Google Scholar 

  • Ozcan E, Notarangelo LD, Geha RS (2008) Primary immune deficiencies with aberrant IgE production. J Allergy Clin Immunol 122:1054–1062. doi:10.1016/j.jaci.2008.10.023, quiz 1063-1054

    Article  CAS  PubMed  Google Scholar 

  • Parronchi P, Macchia D, Piccinni MP, Biswas P, Simonelli C, Maggi E, Ricci M, Ansari AA, Romagnani S (1991) Allergen- and bacterial antigen-specific T-cell clones established from atopic donors show a different profile of cytokine production. Proc Natl Acad Sci U S A 88:4538–4542

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Rapaport MJ, Lebwohl M (2003) Corticosteroid addiction and withdrawal in the atopic: the red burning skin syndrome. Clin Dermatol 21:201–214

    Article  PubMed  Google Scholar 

  • Reid G, Sanders ME, Gaskins HR, Gibson GR, Mercenier A, Rastall R, Roberfroid M, Rowland I, Cherbut C, Klaenhammer TR (2003) New scientific paradigms for probiotics and prebiotics. J Clin Gastroenterol 37:105–118

    Article  PubMed  Google Scholar 

  • Shevchenko A, Shevchenko A (2001) Evaluation of the efficiency of in-gel digestion of proteins by peptide isotopic labeling and MALDI mass spectrometry. Anal Biochem 296:279–283. doi:10.1006/abio.2001.5321

    Article  CAS  PubMed  Google Scholar 

  • Sicherer SH, Leung DY (2009) Advances in allergic skin disease, anaphylaxis, and hypersensitivity reactions to foods, drugs, and insects in 2008. J Allergy Clin Immunol 123:319–327. doi:10.1016/j.jaci.2008.12.025

    Article  PubMed  Google Scholar 

  • Suto H, Matsuda H, Mitsuishi K, Hira K, Uchida T, Unno T, Ogawa H, Ra C (1999) NC/Nga mice: a mouse model for atopic dermatitis. Int Arch Allergy Immunol 120(Suppl 1):70–75. doi:10.1159/000053599

    Article  PubMed  Google Scholar 

  • Tanaka K, Miyake Y, Kiyohara C (2007) Environmental factors and allergic disorders. Allergol Int 56:363–396. doi:10.2332/allergolint.R-07-143

    Article  PubMed  Google Scholar 

  • Uehara M, Izukura R, Sawai T (1990) Blood eosinophilia in atopic dermatitis. Clin Exp Dermatol 15:264–266

    Article  CAS  PubMed  Google Scholar 

  • Umetsu DT, DeKruyff RH (1997) TH1 and TH2 CD4+ cells in human allergic diseases. J Allergy Clin Immunol 100:1–6

    Article  CAS  PubMed  Google Scholar 

  • van Buul-Offers SC, Smink JJ, Gresnigt R, Hamers N, Koedam J, Karperien M (2005) Thyroid hormone, but not parathyroid hormone, partially restores glucocorticoid-induced growth retardation. Pediatr Nephrol 20:335–341. doi:10.1007/s00467-004-1690-y

    Article  PubMed  Google Scholar 

  • van der Aa LB, Lutter R, Heymans HS, Smids BS, Dekker T, van Aalderen WM, Sillevis Smitt JH, Knippels LM, Garssen J, Nauta AJ, Sprikkelman AB, Synbad Study G (2012) No detectable beneficial systemic immunomodulatory effects of a specific synbiotic mixture in infants with atopic dermatitis. Clin Exp Allergy 42:531–539. doi:10.1111/j.1365-2222.2011.03890.x

    Article  PubMed  Google Scholar 

  • Vestergaard C, Yoneyama H, Matsushima K (2000) The NC/Nga mouse: a model for atopic dermatitis. Mol Med Today 6:209–210

    Article  CAS  PubMed  Google Scholar 

  • Wahlgren CF (1999) Itch and atopic dermatitis: an overview. J Dermatol 26:770–779

    Article  CAS  PubMed  Google Scholar 

  • Woodfolk JA (2007) T-cell responses to allergens. J Allergy Clin Immunol 119:280–294. doi:10.1016/j.jaci.2006.11.008, quiz 295-286

    Article  CAS  PubMed  Google Scholar 

  • Yamamoto M, Haruna T, Yasui K, Takahashi H, Iduhara M, Takaki S, Deguchi M, Arimura A (2007) A novel atopic dermatitis model induced by topical application with Dermatophagoides farinae extract in NC/Nga mice. Allergol Int 56:139–148. doi:10.2332/allergolint.O-06-458

    Article  PubMed  Google Scholar 

  • Yesilova Y, Calka O, Akdeniz N, Berktas M (2012) Effect of probiotics on the treatment of children with atopic dermatitis. Ann Dermatol 24:189–193. doi:10.5021/ad.2012.24.2.189

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This research was supported by the grant from the Advanced Technology Center (ATC) Project of the Ministry of Trade, Industry and Energy (N023300019).

Author information

Author notes

    Authors and Affiliations

    1. R&D Center, Cell Biotech, Co., Ltd, 134 Gaegok-Ri Wolgot-Myeon, Gimpo-Si, Gyeonggi-Do, 415-872, Korea

      Min-Soo Kim, Jin-Eung Kim, Yeo-Sang Yoon, Tai Hoon Kim, Jae-Gu Seo, Myung-Jun Chung & Do-Young Yum

    Authors
    1. Min-Soo Kim
      View author publications

      Search author on:PubMed Google Scholar

    2. Jin-Eung Kim
      View author publications

      Search author on:PubMed Google Scholar

    3. Yeo-Sang Yoon
      View author publications

      Search author on:PubMed Google Scholar

    4. Tai Hoon Kim
      View author publications

      Search author on:PubMed Google Scholar

    5. Jae-Gu Seo
      View author publications

      Search author on:PubMed Google Scholar

    6. Myung-Jun Chung
      View author publications

      Search author on:PubMed Google Scholar

    7. Do-Young Yum
      View author publications

      Search author on:PubMed Google Scholar

    Corresponding author

    Correspondence to Do-Young Yum.

    Additional information

    Min-Soo Kim and Jin-Eung Kim contributed equally to this work.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Kim, MS., Kim, JE., Yoon, YS. et al. Improvement of atopic dermatitis-like skin lesions by IL-4 inhibition of P14 protein isolated from Lactobacillus casei in NC/Nga mice. Appl Microbiol Biotechnol 99, 7089–7099 (2015). https://doi.org/10.1007/s00253-015-6455-y

    Download citation

    • Received:

    • Revised:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s00253-015-6455-y

    Keywords