DOI QR코드

DOI QR Code

Immunomodulatory Effects of β-1,3/1,6-glucan and Lactobacillus plantarum LM1004 on Atopic Dermatitis Models

아토피 피부염 모델에 대한 β-1,3/1,6-glucan과 Lactobacillus plantarum LM1004의 면역 조절 효과

  • Kim, In Sung (Department of Animal Resources Technology, Gyeongnam National University of Science and Technology) ;
  • Kim, Sung Hak (Department of Animal Science, Chonnam National University) ;
  • Kim, Jeong A (Department of Animal Resources Technology, Gyeongnam National University of Science and Technology) ;
  • Yu, Da Yoon (Department of Animal Resources Technology, Gyeongnam National University of Science and Technology) ;
  • Kim, Gwang Il (Department of Animal Resources Technology, Gyeongnam National University of Science and Technology) ;
  • Park, Dong-Chan (Glucan Corporation) ;
  • Lim, Jong Min (Glucan Corporation) ;
  • Lee, Sang Suk (Department of Animal Science and Technology, Sunchon National University) ;
  • Choi, In Soon (Departmnet of Life Science, Silla University) ;
  • Cho, Kwang Keun (Department of Animal Resources Technology, Gyeongnam National University of Science and Technology)
  • 김인성 (경남과학기술대학교 동물소재공학과) ;
  • 김성학 (전남대학교 동물자원학부) ;
  • 김정아 (경남과학기술대학교 동물소재공학과) ;
  • 유다윤 (경남과학기술대학교 동물소재공학과) ;
  • 김광일 (경남과학기술대학교 동물소재공학과) ;
  • 박동찬 ((주)글루칸) ;
  • 임종민 ((주)글루칸) ;
  • 이상석 (순천대학교 동물자원과학과) ;
  • 최인순 (신라대학교 생명과학과) ;
  • 조광근 (경남과학기술대학교 동물소재공학과)
  • Received : 2017.09.29
  • Accepted : 2018.01.08
  • Published : 2018.01.30

Abstract

In this study, we examined the efficacy of the immune regulation of ${\beta}$-1,3/1,6-glucan and Lactobacillus plantarum LM1004 on atopic dermatitis models. The oral administration of ${\beta}$-1,3/1,6-glucan and L. plantarum LM1004 on mice significantly decreased the amount of scratching, leakage to evans blue, and concentrations of serum immunoglobulin E (IgE) and histamine compared with the atopic dermatitis - induced group. When atopic dermatitis was induced, the transcription factors (GATA-3, retinoic acid-related orphan receptor ${\gamma}$ T [$ROR{\gamma}T$]) and cytokines (interleukin-4 [IL-4], IL-17) of Th2 and Th17 cells were overexpressed at the transcriptional level, and they significantly decreased with oral administration of ${\beta}$-1,3/1,6-glucan and L. plantarum LM1004. In addition, ${\beta}$-1,3/1,6-glucan and L. plantarum LM1004 were shown to modulate the immune balance by increasing the expression of Th1 and Treg transcription (T-bet, forkhead box p3 [Foxp3]) and cytokines (interferon-${\gamma}$ [IFN-${\gamma}$], transforming growth factor-${\beta}$ [TGF-${\beta}$]). Galectin-9 and filaggrin were significantly lower in the atopic dermatitis - induced group and significantly higher in the ${\beta}$-1,3/1,6-glucan-treated group. In contrast, thymic stromal lymphopoietin (TSLP) was highest in the atopic dermatitis-induced group, while mice that were orally administered ${\beta}$-1,3/1,6-glucan and L. plantarum LM1004 showed similar TSLP levels to the control group. These results indicate that ${\beta}$-1,3/1,6-glucan and L. plantarum LM1004 have immunomodulatory effects and atopic dermatitis improvement effects in an animal model of atopic dermatitis. Therefore, it is expected that ${\beta}$-1,3/1,6-glucan and L. plantarum LM1004 can be used as natural materials in the treatment of atopic dermatitis.

본 연구에서는 아토피 피부염 동물 모델에 대한 ${\beta}$-1,3/1,6-glucan과 L. plantarum LM1004의 면역조절 효과를 확인하고자 하였다. 가려움증의 횟수와 유출된 evans blue, 그리고 혈청 IgE와 histamine의 농도는 ${\beta}$-1,3/1,6-glucan과 L. plantarum LM1004를 섭취한 그룹에서 아토피 피부염 유발그룹에 비해 유의적으로 감소하는 결과를 나타내었다. 아토피 피부염이 유발되면 전사 수준에서 Th2 및 Th17 세포의 전사인자 및 cytokine은 과발현되며, ${\beta}$-1,3/1,6-glucan과 L. plantarum LM1004를 섭취하였을 때 이를 유의적으로 감소되었다. 또한 ${\beta}$-1,3/1,6-glucan과 L. plantarum LM1004는 Th1 및 Treg 세포의 전사인자(T-bet, GATA-3, $ROR{\gamma}T$, Foxp3) 및 cytokine (INF-${\gamma}$, IL-4, IL-17, TGF-${\beta}$)의 발현을 증가시킴으로써 면역 균형을 조절하는 것으로 나타났다. Galectin-9과 filaggrin은 아토피피부염 유발 처리군에서 유의적으로 가장 낮았으며, ${\beta}$-1,3/1,6-glucan 처리군에서 유의적으로 가장 높게 나타났다. 이와 반대로 TSLP는 아토피 피부염 유발그룹에서 유의적으로 가장 높았으며 ${\beta}$-1,3/1,6-glucan과 L. plantarum LM1004를 섭취한 그룹은 대조군과 유사한 수준이었다. 이러한 결과를 통해 ${\beta}$-1,3/1,6-glucan과 L. plantarum LM1004는 아토피 피부염 동물 모델에서 면역조절 작용 및 아토피 피부염의 개선 효과를 가짐을 알 수 있었다. 따라서 ${\beta}$-1,3/1,6-glucan과 L. plantarum LM1004는 아토피 피부염에 유용한 천연소재로서 사용될 것으로 기대된다.

Keywords

References

  1. Allerano, F. M., Wetworth, C. E., Arana, A., Fernandez, C. and Paul, C. F. 2007. Risk of lymphoma following exposure to calcineurin inhibitors and topical steroids in patients with atopic dermatitis. J. Invest. Dermatol. 127, 808-816. https://doi.org/10.1038/sj.jid.5700622
  2. Babicek, K., Cechova, I., Simon, R. R., Harwood, M. and Cox, D. J. 2007. Toxicological assessment of a particulate yeast (1,3/1,6)-beta-D-glucan in rats. Food Chem. Toxicol. 45, 1719-1730. https://doi.org/10.1016/j.fct.2007.03.013
  3. Bedoya, S. K., Lam, B., Lau, K. and Larkin, J., 3rd. 2013. Th17 cells in immunity and autoimmunity. Clin. Dev. Immunol. 2013, 1-16.
  4. Belardelli, F. 1995. Role of interferons and other cytokines in the regulation of the immune response. APMIS 103, 161-179. https://doi.org/10.1111/j.1699-0463.1995.tb01092.x
  5. Bobek, P. and Galbavy, S. 2001. Effect of pleuran (beta-glucan from Pleurotus ostreatus) on the antioxidant status of the organism and on dimethylhydrazine-induced precancerous lesions in rat colon. Br. J. Biomed. Sci. 58, 164-168.
  6. Chan, G. C., Chan, W. K. and Sze, D. M. 2009. The effects of beta-glucan on human immune and cancer cells. J. Hematol. Oncol. 2, doi: 10.1186/1756-8722-2-25.
  7. Choi, Y., Kim, M. S. and Hwang, J. K. 2012. Inhibitory effects of panduratin A on allergy-related mediator production in rat basophilic leukemia mast cells. Inflammation 35, 1904- 1915. https://doi.org/10.1007/s10753-012-9513-y
  8. Chomczynski, P. and Sacchi, N. 1987. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenolchloroform extraction. Anal. Biochem. 162, 156-159.
  9. Dai, S. Y., Nakagawa, R., Itoh, A., Murakami, H., Kashio, Y., Abe, H., Katoh, S., Kontani, K., Kihara, M., Zhang, S. L., Hata, T., Nakamura, T., Yamauchi, A. and Hirashima, M. 2005. Galectin-9 induces maturation of human monocyte- derived dendritic cells. J. Immunol. 175, 2974-2981. https://doi.org/10.4049/jimmunol.175.5.2974
  10. de Kivit, S., Saeland, E., Kraneveld, A. D., vande Kant, H. J., Schouten, B., van Esch, B. C., Knol, J., Sprikkelman, A. B., van der Aa, L. B., Knippels, L. M., Garssen, J., van Kooyk, Y. and Willemsen, L. E. 2012. Galectin-9 induced by dietary synbiotics is involved in suppression of allergic symptoms in mice and humans. Allergy 67, 343-352. https://doi.org/10.1111/j.1398-9995.2011.02771.x
  11. Delaney, B., Nicolosi, R. J., Wilson, T. A., Carlson, T., Frazer, S., Zheng, G. H., Hess, R., Ostergren, K., Haworth, J. and Knutson, N. 2003. Beta-glucan fractions from barley and oats are similarly antiatherogenic in hypercholesterolemic syrian golden hamsters. J. Nutr. 133, 468-475. https://doi.org/10.1093/jn/133.2.468
  12. Delatte, S. J., Evans, J., Hebra, A., Adamson, W., Othersen, H. B. and Tagge, E. P. 2001. Effectiveness of beta-glucan collagen for treatment of partical-thickness burns in children. J. Pediatr. Surg. 36, 113-118. https://doi.org/10.1053/jpsu.2001.20024
  13. Duncan, D. B. 1955. Multiple range and multiple F tests. Biometrics 11, 1-42. https://doi.org/10.2307/3001478
  14. Fujiwara, D., Inoue, S., Wakabayashi, H. and 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. https://doi.org/10.1159/000081305
  15. Furue, M., Chiba, T., Tsuji, G., Ulzii, D., Kido-Nakahara, M., Nakahara, T. and Kadono, T. 2017. Atopic dermatitis: immune deviation, barrier dysfunction, IgE autoreactivity and new therapies. Allergol. Int. 66, 1-6. https://doi.org/10.1016/j.alit.2016.11.004
  16. Hetland, G., Ohno, N., Aaberge, I. S. and Lovik, M. 2000. Protective effect of ${\beta}$-glucan against systemic Streptococcus pneumonia infection in mice. FEMS Immunol. Med. Microbiol. 27, 111-116.
  17. Inagaki, N., Miura, T., Nagai, H., Ono, Y. and Koda, A. 1988. Inhibition of vascular permeability increase in mice. An additional anti-allergic mechanism of glucocorticoids. Int. Arch. Allergy Appl. Immunol. 87, 254-259. https://doi.org/10.1159/000234681
  18. Ishiguro, K., Oku, H., Suitani, A. and Yamamoto, Y. 2002. Effects of conjugated linoleic acid on anaphylaxis and allergic pruritus. Biol. Pharm. Bull. 25, 1655-1657. https://doi.org/10.1248/bpb.25.1655
  19. Jo, Y. R. and Kang, S. M. 2012. Lactococcus lactis culture method for enhanced depression of inducer in atopic diseases. Kor. J. Microbiol. Biotechnol. 40, 310-318. https://doi.org/10.4014/kjmb.1205.05025
  20. Kalliomaki, M. and Isolauri, E. 2003. Role of intestinal flora in the development of allergy. Curr. Opin. Allergy Clin. Immunol. 3, 15-20. https://doi.org/10.1097/00130832-200302000-00003
  21. 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 syndromelike 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
  22. Katayama, S., Shionoya, H. and Ohtake, S. 1978. A new method for extraction of extravasated dye in the skin and the influence of fasting stress on passive cutaneous anaphylaxis in guinea pigs and rate. Microbiol. Immunol. 22, 89-101. https://doi.org/10.1111/j.1348-0421.1978.tb00352.x
  23. Kim, H. J., Kim, Y. J., Lee, S. H., Yu, J., Jeong, S. K. and Hong, S. J. 2014. Effects of Lactobacillus rhamnosus on allergic march model by suppressing Th2, Th17, and TSLP responses via $CD4^+$ $CD25^+$ $Foxp3^+$ Tregs. Clin. Immunol. 153, 178-186. https://doi.org/10.1016/j.clim.2014.04.008
  24. Kim, J. H., Kim, M. R., Lee, J. H., Lee, J. W. and Kim, S. K. 2000. Production of high molecular weight pullulan by Aureobasidium pullulans using glucosamine. Biotechnol. Lett. 22, 987-990. https://doi.org/10.1023/A:1005681019573
  25. Klein, G., Pack, A., Bonaparte, C. and Reuter, G. 1998. Taxonomy and phsiology of probiotic lactic acid bacteria. Int. J. Food Microbiol. 41, 103-125. https://doi.org/10.1016/S0168-1605(98)00049-X
  26. Kraus, J. Blaschek, W., Schutz, M. and Franz, G. 1992. Antitumor activity of cell wall ${\beta}$-1,3/1,6-glucans from Phytophthora species. Planta. Medica. 58, 39-42. https://doi.org/10.1055/s-2006-961386
  27. Lee, G. S., Jung, H. M., Oh, S. K., Cheong, J. H. and Kang, T. J. 2012. Effects of herbal complex on atopic dermatitis in BALB/c mice. Kor. J. Pharmacogn. 43, 59-65.
  28. 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. https://doi.org/10.1172/JCI21060
  29. Liu, F. T., Patterson, R. J. and Wang, J. L. 2002. Intracellular functions of galectins. Biochim. Biophys. Acta. 1572, 263-273. https://doi.org/10.1016/S0304-4165(02)00313-6
  30. Lugovic, L., Lipozencic, J. and Jakic-Razumovic, J. 2005. Prominent involvement of activated Th1-subset of T-cells and increased expression of receptor for IFN-gamma on keratinocytes in atopic dermatitis acute skin lesions. Int. Arch. Allergy Immunol. 137, 125-133. https://doi.org/10.1159/000085468
  31. Matsui, K. and Nishikawa, A. 2013. Peptidoglycan-induced T helper 2 immune response in mice involves interleukin-10 secretion from langerhans cells. Microbiol. Immunol. 57, 130-138. https://doi.org/10.1111/j.1348-0421.2012.12006.x
  32. Mclntosh, M., Stone, B. A. and Stanisich, V. A. 2005. Curdlan and other bacterial (1$\rightarrow$3)-beta-D-glucans. Appl. Microbiol. Biotechnol. 68, 163-173. https://doi.org/10.1007/s00253-005-1959-5
  33. Mercenier, A., Pavan, S. and Pot, B. 2003. Probiotics as biotherapeutic agents: present knowledge and future prospects. Curr. Pharm. Des. 9, 175-191. https://doi.org/10.2174/1381612033392224
  34. Metcalfe, D. D., Kaliner, M. and Donlon, M. A. 1981. The mast cell. Crit. Rev. Immunol. 3, 23-74.
  35. Miyajima, I., Dombrowicz, D., Martin, T. R., Ravetch, J. V., Kinet, J. P. and Galli, S. J. 1997. Systemic anaphylaxis in the mouse can be mediated largely through IgG1 and Fc gammaR III. Assessment of the cardiopulmonary changes, mast cell degranulation, and death associated with active or IgE- or IgG1-dependent passive anaphylaxis. J. Clin. Invest. 99, 901-914. https://doi.org/10.1172/JCI119255
  36. Naidu, A. S., Bidlack, W. R. and Clemens, R. A. 1999. Probiotic spectra of lactic acid bacteria (LAB). Crit. Rev. Food Sci. Nutr. 39, 13-126. https://doi.org/10.1080/10408699991279187
  37. Nicolosi, R., Bell, S. J., Bistrian, B. R., Greenberg, I., Forse, R. A. and Blackburn, G. L. 1999. Plasma lipid changes after supplementation with beta-glucan fiber from yeast. Am. J. Clin. Nutr. 70, 208-212. https://doi.org/10.1093/ajcn.70.2.208
  38. Noda, S., Krueger, J. G. and Guttman-Yassky, E. 2015. The translational revolution and use of biologics in patients with inflammatory skin diseases. J. Allergy Clin. Immunol. 135, 324-336. https://doi.org/10.1016/j.jaci.2014.11.015
  39. Nograles, K. E., Zaba, L. C., Guttman-Yassky, E., Fuentes- Duculan, J., Suarez-Farinas, M., Cardinale, I., Khatcherian, A., Gonzalez, J., Pierson, K. C., White, T. R., Pensabene, C., Coats, I., Novitskaya, I., Lowes, M. A. and Krueger, J. G. 2008. Th17 cytokines interleukin (IL)-17 and IL-22 modulate distinct inflammatory and keratinocyte-response pathways. Br. J. Dermatol. 159, 1092-1102.
  40. Ohtsuka, E., Kawai, S., Ichikawa, T., Nojima, H., Kitagawa, K., Shirai, Y., Kamimura, K. and Kuraishi, Y. 2001. Roles of mast cells and histamine in mosquito bite-induced allergic itch-associated response in mice. Jpn. J. Pharmacol. 86, 97-105. https://doi.org/10.1254/jjp.86.97
  41. Palomeres, O., Yaman, G., Azkur, A. K., Akkoc, T., Akdis, M. and Akdis, C. A. 2010. Role of Treg in immune regulation of allergic diseases. Eur. J. Immunol. 40, 1232-1240. https://doi.org/10.1002/eji.200940045
  42. Peng, G. C. and Hsu, C. H. 2005. The efficacy and safety of heat-killed Lactobacillus paracasie for treatment of perennial allergic rhinitis induced by house-dust mite. Pediatr. Allergy Immunol. 16, 433-438. https://doi.org/10.1111/j.1399-3038.2005.00284.x
  43. Prescott, S. L., Dunstan, J. A., Hale, J., Breckler, L., Lehmann, H., Weston, S. and Richmond, P. 2005. Clinical effects of probiotics are associated with increased interferon-gamma responses in very young children with atopic dermatitis. Clin. Exp. Allergy 35, 1557-1564. https://doi.org/10.1111/j.1365-2222.2005.02376.x
  44. Rabinovich, G. A., Liu, F. T., Hirashima, M. and Anderson, A. 2007. An emerging role for galectins in tuning the immune response: lessons from experimental models of inflammatory disease, autoimmunity and cancer. Scand J. Immunol. 66, 143-158. https://doi.org/10.1111/j.1365-3083.2007.01986.x
  45. Romagnani, S. 2000. T-cell subsets (Th1 versus Th2). Ann. Allergy Asthma. Immunol. 85, 9-18. https://doi.org/10.1016/S1081-1206(10)62426-X
  46. Rothschild, A. M., Gomes, E. L. and Rossi, M. A. 1991. Reversible rat mesenteric mast cell swelling caused by vagal stimulation or sham-feeding. Agents Actions 34, 295-301. https://doi.org/10.1007/BF01988719
  47. Sano, Y., Masuda, K., Tamagawa-Mineoka, R., Matsunaka, H., Murakami, Y., Yamashita, R., Morita, E. and Katoh, N. 2013. Thymic stromal lymphopoietin expression is increased in the horny layer of patients with atopic dermatitis. Clin. Exp. Immunol. 171, 330-337. https://doi.org/10.1111/cei.12021
  48. Schroeder, J. T. 2011. Basophils: emerging roles in the pathogenesis of allergic disease. Immunol. Rev. 242, 144-160. https://doi.org/10.1111/j.1600-065X.2011.01023.x
  49. Seki, M., Oomizu, S., Sakata, K. M., Sakata, A., Arikawa, T., Watanabe, K., Ito, K., Takeshita, K., Niki, T., Saita, N., Nishi, N., Yamauchi, A., Katoh, S., Matsukawa, A., Kuchroo, V. and Hirashima, M. 2008. Galectin-9 suppresses the generation of Th17, promotes the induction of regulatory T cells, and regulates experimental autoimmune arthritis. Clin. Immunol. 127, 78-88. https://doi.org/10.1016/j.clim.2008.01.006
  50. Seo, H. P., Kim, J. M., Shin, H. D., Kim, T. K., Chang, H. J., Park, B. R. and Lee, J. W. 2002. Production of ${\beta}$- 1,3/1,6-glucan by Aureobasidium pullulans SM-2001. Kor. J. Biotechnol. Bioeng. 17, 376-380.
  51. Soumelis, V., Reche, P. A., Kanzler, H., Yuan, W., Edward, G., Homey, B., Gilliet, M., Ho, S., Antonenko, S., Lauerma, A., Smith, K., Gorman, D., Zurawski, S., Abrams, J., Menon, S., McClanahan, T., de Waal-Malefyt, Rd. R., Bazan, F., Kastelein, R. A. and Liu, Y. J. 2002. Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP. Nat. Immunol. 3, 673-680.
  52. Tokunaka, K., Ohno, N., Adachi, Y., Miura, N. N. and Yadomae, T. 2002. Application of Candida solubilized cell wall ${\beta}$-glucan in antitumor immunotherapy against P815 mastocytoma in mice. Int. Immunopharmacol. 2, 59-67. https://doi.org/10.1016/S1567-5769(01)00148-5
  53. Vitaliti, G., Pavone, P., Guglielmo, F., Spataro, G. and Falsaperla, R. 2014. The immunomodulatory effect of probiotics beyond atopy: an update. J. Asthma. 51, 320-332. https://doi.org/10.3109/02770903.2013.862259
  54. Young, C. A., Rorke, E. A., Adhikary, G., Xu, W. and Eckert, R. L. 2017. Loss of epidermal AP1 transcription factor function reduces filaggrin level, alters chemokine expression and produces an ichthyosis-related phenotype. Cell Death Dis. 8, e2840. https://doi.org/10.1038/cddis.2017.238