Open Access

Therapeutic effects of bee venom on experimental atopic dermatitis

  • Authors:
    • Hyemin Gu
    • Woon‑Hae Kim
    • Hyun‑Jin An
    • Jung‑Yeon Kim
    • Mi‑Gyeong Gwon
    • Sang Mi Han
    • Jaechan Leem
    • Kwan‑Kyu Park
  • View Affiliations

  • Published online on: August 17, 2018     https://doi.org/10.3892/mmr.2018.9398
  • Pages: 3711-3718
  • Copyright: © Gu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Atopic dermatitis (AD) is a chronic skin inflammatory disease characterized by recurrent eczema and itching. It is caused by a poorly controlled immune response and damage to the skin barrier. Purified bee venom (BV) is a natural toxin produced by honeybees (Apis mellifera L.), and is well known for its anti‑inflammatory, analgesic and anti‑cancer effects against various types of disease. However, treatment strategies based on anti‑inflammatory properties have not been adequately studied in AD. Thus, the present study examined the progression of AD‑like skin lesions induced by ovalbumin (OVA) and the mechanism of action of BV. BV, administered by intraperitoneal inoculation, was observed to reduce the symptoms of AD, in addition to the serum immunoglobulin E levels, according to dorsal skin thickness and histopathologic analysis. The treatment also inhibited the infiltration of eosinophils and mast cells. These results suggested that it is possible to develop novel AD alternative therapy using BV by effectively suppressing allergic skin inflammation in AD.

References

1 

Leung DY and Guttman-Yassky E: Deciphering the complexities of atopic dermatitis: Shifting paradigms in treatment approaches. J Allergy Clin Immunol. 134:769–779. 2014. View Article : Google Scholar : PubMed/NCBI

2 

Schlapbach C and Simon D: Update on skin allergy. Allergy. 69:1571–1581. 2014. View Article : Google Scholar : PubMed/NCBI

3 

Lim SJ, Kim M, Randy A, Nam EJ and Nho CW: Effects of Hovenia dulcis Thunb. extract and methyl vanillate on atopic dermatitis-like skin lesions and TNF-α/IFN-γ-induced chemokines production in HaCaT cells. J Pharm Pharmacol. 68:1465–1479. 2016. View Article : Google Scholar : PubMed/NCBI

4 

Galli SJ, Tsai M and Piliponsky AM: The development of allergic inflammation. Nature. 454:445–454. 2008. View Article : Google Scholar : PubMed/NCBI

5 

Owen CE: Immunoglobulin E: Role in asthma and allergic disease: Lessons from the clinic. Pharmacol Ther. 113:121–133. 2007. View Article : Google Scholar : PubMed/NCBI

6 

Kawakami T, Ando T, Kimura M, Wilson BS and Kawakami Y: Mast cells in atopic dermatitis. Curr Opin Immunol. 21:666–678. 2009. View Article : Google Scholar : PubMed/NCBI

7 

Stone KD, Prussin C and Metcalfe DD: IgE, mast cells, basophils, and eosinophils. J Allergy Clin Immunol. 125 2 Suppl 2:S73–S80. 2010. View Article : Google Scholar : PubMed/NCBI

8 

Kempuraj D, Castellani ML, Petrarca C, Frydas S, Conti P, Theoharides TC and Vecchiet J: Inhibitory effect of quercetin on tryptase and interleukin-6 release, and histidine decarboxylase mRNA transcription by human mast cell-1 cell line. Clin Exp Med. 6:150–156. 2006. View Article : Google Scholar : PubMed/NCBI

9 

Leung DY, Boguniewicz M, Howell MD, Nomura I and Hamid QA: New insights into atopic dermatitis. J Clin Invest. 113:651–657. 2004. View Article : Google Scholar : PubMed/NCBI

10 

Miazgowicz MM, Headley MB, Larson RP and Ziegler SF: Thymic stromal lymphopoietin and the pathophysiology of atopic disease. Expert Rev Clin Immunol. 5:547–556. 2009. View Article : Google Scholar : PubMed/NCBI

11 

Ziegler SF: The role of thymic stromal lymphopoietin (TSLP) in allergic disorders. Curr Opin Immunol. 22:795–799. 2010. View Article : Google Scholar : PubMed/NCBI

12 

Wilson SR, Thé L, Batia LM, Beattie K, Katibah GE, McClain SP, Pellegrino M, Estandian DM and Bautista DM: The epithelial cell-derived atopic dermatitis cytokine TSLP activates neurons to induce itch. Cell. 155:285–295. 2013. View Article : Google Scholar : PubMed/NCBI

13 

Soumelis V, Reche PA, Kanzler H, Yuan W, Edward G, Homey B, Gilliet M, Ho S, Antonenko S, Lauerma A, et al: Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP. Nat Immunol. 3:673–680. 2002. View Article : Google Scholar : PubMed/NCBI

14 

Watanabe N, Hanabuchi S, Soumelis V, Yuan W, Ho S, de Waal Malefyt R and Liu YJ: Human thymic stromal lymphopoietin promotes dendritic cell-mediated CD4+ T cell homeostatic expansion. Nat Immunol. 5:426–434. 2004. View Article : Google Scholar : PubMed/NCBI

15 

Ebner S, Nguyen VA, Forstner M, Wang YH, Wolfram D, Liu YJ and Romani N: Thymic stromal lymphopoietin converts human epidermal Langerhans cells into antigen-presenting cells that induce proallergic T cells. J Allergy Clin Immunol. 119:982–990. 2007. View Article : Google Scholar : PubMed/NCBI

16 

Wang Q, Du J, Zhu J, Yang X and Zhou B: Thymic stromal lymphopoietin signaling in CD4(+) T cells is required for TH2 memory. J Allergy Clin Immunol. 135:781–791.e3. 2015. View Article : Google Scholar : PubMed/NCBI

17 

Kim BS, Siracusa MC, Saenz SA, Noti M, Monticelli LA, Sonnenberg GF, Hepworth MR, Van Voorhees AS, Comeau MR and Artis D: TSLP elicits IL-33-independent innate lymphoid cell responses to promote skin inflammation. Sci Transl Med. 5:170ra162013. View Article : Google Scholar : PubMed/NCBI

18 

Cabanillas B and Novak N: Atopic dermatitis and filaggrin. Curr Opin Immunol. 42:1–8. 2016. View Article : Google Scholar : PubMed/NCBI

19 

Levin J, Friedlander SF and Del Rosso JQ: Atopic dermatitis and the stratum corneum: Part 1: The role of filaggrin in the stratum corneum barrier and atopic skin. J Clin Aesthet Dermatol. 6:16–22. 2013.PubMed/NCBI

20 

Son DJ, Lee JW, Lee YH, Song HS, Lee CK and Hong JT: Therapeutic application of anti-arthritis, pain-releasing, and anti-cancer effects of bee venom and its constituent compounds. Pharmacol Ther. 115:246–270. 2007. View Article : Google Scholar : PubMed/NCBI

21 

Billingham ME, Morley J, Hanson JM, Shipolini RA and Vernon CA: Letter: An anti-inflammatory peptide from bee venom. Nature. 245:163–164. 1973. View Article : Google Scholar : PubMed/NCBI

22 

Kwon YB, Lee HJ, Han HJ, Mar WC, Kang SK, Yoon OB, Beitz AJ and Lee JH: The water-soluble fraction of bee venom produces antinociceptive and anti-inflammatory effects on rheumatoid arthritis in rats. Life Sci. 71:191–204. 2002. View Article : Google Scholar : PubMed/NCBI

23 

Kwon YB, Lee JD, Lee HJ, Han HJ, Mar WC, Kang SK, Beitz AJ and Lee JH: Bee venom injection into an acupuncture point reduces arthritis associated edema and nociceptive responses. Pain. 90:271–280. 2001. View Article : Google Scholar : PubMed/NCBI

24 

Stieger M, Wüthrich B, Wyss S and Kopper E: Clinical picture and diagnosis of bee-venom allergy. A comparison between skin tests and RAST determinations. Hautarzt. 29:632–637. 1978.(In German).

25 

Ip SW, Liao SS, Lin SY, Lin JP, Yang JS, Lin ML, Chen GW, Lu HF, Lin MW, Han SM and Chung JG: The role of mitochondria in bee venom-induced apoptosis in human breast cancer MCF7 cells. In Vivo. 22:237–245. 2008.PubMed/NCBI

26 

Oršolić N: Bee venom in cancer therapy. Cancer Metastasis Rev. 31:173–194. 2012. View Article : Google Scholar : PubMed/NCBI

27 

Park MH, Choi MS, Kwak DH, Oh KW, Yoon DY, Han SB, Song HS, Song MJ and Hong JT: Anti-cancer effect of bee venom in prostate cancer cells through activation of caspase pathway via inactivation of NF-κB. Prostate. 71:801–812. 2011. View Article : Google Scholar : PubMed/NCBI

28 

Kim WH, An HJ, Kim JY, Gwon MG, Gu H, Jeon M, Sung WJ, Han SM, Pak SC, Kim MK and Park KK: Beneficial effects of melittin on ovalbumin-induced atopic dermatitis in mouse. Sci Rep. 7:176792017. View Article : Google Scholar : PubMed/NCBI

29 

Han SM, Lee GG and Park KK: Acute dermal toxicity study of bee venom (Apis mellifera L.) in rats. Toxicol Res. 28:99–102. 2012. View Article : Google Scholar : PubMed/NCBI

30 

Dombrowski Y, Peric M, Koglin S, Kaymakanov N, Schmezer V, Reinholz M, Ruzicka T and Schauber J: Honey bee (Apis mellifera) venom induces AIM2 inflammasome activation in human keratinocytes. Allergy. 67:1400–1407. 2012. View Article : Google Scholar : PubMed/NCBI

31 

Kim JY, Lee WR, Kim KH, An HJ, Chang YC, Han SM, Park YY, Pak SC and Park KK: Effects of bee venom against Propionibacterium acnes-induced inflammation in human keratinocytes and monocytes. Int J Mol Med. 35:1651–1656. 2015. View Article : Google Scholar : PubMed/NCBI

32 

Lee WR, Kim SJ, Park JH, Kim KH, Chang YC, Park YY, Lee KG, Han SM, Yeo JH, Pak SC and Park KK: Bee venom reduces atherosclerotic lesion formation via anti-inflammatory mechanism. Am J Chin Med. 38:1077–1092. 2010. View Article : Google Scholar : PubMed/NCBI

33 

Han S, Lee K, Yeo J, Baek H and Park K: Antibacterial and anti-inflammatory effects of honeybee (Apis mellifera) venom against acne-inducing bacteria. J Med Plants Res. 4:459–464. 2010.

34 

Lee YJ, Kim JE, Kwak MH, Go J, Kim DS, Son HJ and Hwang DY: Quantitative evaluation of the therapeutic effect of fermented soybean products containing a high concentration of GABA on phthalic anhydride-induced atopic dermatitis in IL-4/Luc/CNS-1 Tg mice. Int J Mol Med. 33:1185–1194. 2014. View Article : Google Scholar : PubMed/NCBI

35 

van den Oord RA and Sheikh A: Filaggrin gene defects and risk of developing allergic sensitisation and allergic disorders: Systematic review and meta-analysis. BMJ. 339:b24332009. View Article : Google Scholar : PubMed/NCBI

36 

Cha HY, Ahn SH, Cheon JH, Park SY and Kim K: Hataedock treatment has preventive therapeutic effects for atopic dermatitis through skin barrier protection in Dermatophagoides farinae-induced NC/Nga mice. J Ethnopharmacol. 206:327–336. 2017. View Article : Google Scholar : PubMed/NCBI

37 

Amin K: The role of mast cells in allergic inflammation. Respir Med. 106:9–14. 2012. View Article : Google Scholar : PubMed/NCBI

38 

Choi EJ, Debnath T, Tang Y, Ryu YB, Moon SH and Kim EK: Topical application of Moringa oleifera leaf extract ameliorates experimentally induced atopic dermatitis by the regulation of Th1/Th2/Th17 balance. Biomed Pharmacother. 84:870–877. 2016. View Article : Google Scholar : PubMed/NCBI

39 

Liu FT, Goodarzi H and Chen HY: IgE, mast cells, and eosinophils in atopic dermatitis. Clin Rev Allergy Immunol. 41:298–310. 2011. View Article : Google Scholar : PubMed/NCBI

40 

Sae-Wong C, Mizutani N, Kangsanant S and Yoshino S: Topical skin treatment with Fab fragments of an allergen-specific IgG1 monoclonal antibody suppresses allergen-induced atopic dermatitis-like skin lesions in mice. Eur J Pharmacol. 779:131–137. 2016. View Article : Google Scholar : PubMed/NCBI

41 

An HJ, Lee WR, Kim KH, Kim JY, Lee SJ, Han SM, Lee KG, Lee CK and Park KK: Inhibitory effects of bee venom on Propionibacterium acnes-induced inflammatory skin disease in an animal model. Int J Mol Med. 34:1341–1348. 2014. View Article : Google Scholar : PubMed/NCBI

42 

You CE, Moon SH, Lee KH, Kim KH, Park CW, Seo SJ and Cho SH: Effects of emollient containing bee venom on atopic dermatitis: A double-blinded, randomized, base-controlled, multicenter study of 136 patients. Ann Dermatol. 28:593–599. 2016. View Article : Google Scholar : PubMed/NCBI

43 

Liu YJ: Thymic stromal lymphopoietin: Master switch for allergic inflammation. J Exp Med. 203:269–273. 2006. View Article : Google Scholar : PubMed/NCBI

44 

Comeau MR and Ziegler SF: The influence of TSLP on the allergic response. Mucosal Immunol. 3:138–147. 2010. View Article : Google Scholar : PubMed/NCBI

45 

Jeong HJ, Hong SH, Lee DJ, Park JH, Kim KS and Kim HM: Role of Ca(2+) on TNF-alpha and IL-6 secretion from RBL-2H3 mast cells. Cell Signal. 14:633–639. 2002. View Article : Google Scholar : PubMed/NCBI

46 

Han NR, Moon PD, Kim HM and Jeong HJ: Tryptanthrin ameliorates atopic dermatitis through down-regulation of TSLP. Arch Biochem Biophys. 542:14–20. 2014. View Article : Google Scholar : PubMed/NCBI

47 

Solovjov DA, Pluskota E and Plow EF: Distinct roles for the alpha and beta subunits in the functions of integrin alphaMbeta2. J Biol Chem. 280:1336–1345. 2005. View Article : Google Scholar : PubMed/NCBI

Related Articles

Journal Cover

October 2018
Volume 18 Issue 4

Print ISSN: 1791-2997
Online ISSN:1791-3004

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Gu, H., Kim, W., An, H., Kim, J., Gwon, M., Han, S.M. ... Park, K. (2018). Therapeutic effects of bee venom on experimental atopic dermatitis. Molecular Medicine Reports, 18, 3711-3718. https://doi.org/10.3892/mmr.2018.9398
MLA
Gu, H., Kim, W., An, H., Kim, J., Gwon, M., Han, S. M., Leem, J., Park, K."Therapeutic effects of bee venom on experimental atopic dermatitis". Molecular Medicine Reports 18.4 (2018): 3711-3718.
Chicago
Gu, H., Kim, W., An, H., Kim, J., Gwon, M., Han, S. M., Leem, J., Park, K."Therapeutic effects of bee venom on experimental atopic dermatitis". Molecular Medicine Reports 18, no. 4 (2018): 3711-3718. https://doi.org/10.3892/mmr.2018.9398