The Korean Journal of Physiology and Pharmacology

  • 제26권4호
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  • Pages.287-295
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  • 2022
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  • 1226-4512(pISSN)
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  • 2093-3827(eISSN)
대한약리학회 (The Korean Society of Pharmacology)
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Adipose-derived stem cells decolonize skin Staphylococcus aureus by enhancing phagocytic activity of peripheral blood mononuclear cells in the atopic rats

  • Lee, Jaehee (Neuroscience Research Institute and Department of Physiology, Korea University College of Medicine) ;
  • Park, Leejin (Glovi Plastic Surgery) ;
  • Kim, Hyeyoung (Neuroscience Research Institute and Department of Physiology, Korea University College of Medicine) ;
  • Rho, Bong-il (Glovi Plastic Surgery) ;
  • Han, Rafael Taeho (Neuroscience Research Institute and Department of Physiology, Korea University College of Medicine) ;
  • Kim, Sewon (Department of Microbiology, Korea University College of Medicine) ;
  • Kim, Hee Jin (Division of Biological Science and Technology, Science and Technology College, Yonsei University Mirae Campus) ;
  • Na, Heung Sik (Neuroscience Research Institute and Department of Physiology, Korea University College of Medicine) ;
  • Back, Seung Keun (Department of Biomedical Laboratory Science, College of Medical Science, Konyang University)
  • 투고 : 2022.05.09
  • 심사 : 2022.06.16
  • 발행 : 2022.07.01
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초록

Staphylococcus aureus (S. aureus) is known to induce apoptosis of host immune cells and impair phagocytic clearance, thereby being pivotal in the pathogenesis of atopic dermatitis (AD). Adipose-derived stem cells (ASCs) exert therapeutic effects against inflammatory and immune diseases. In the present study, we investigated whether systemic administration of ASCs restores the phagocytic activity of peripheral blood mononuclear cells (PBMCs) and decolonizes cutaneous S. aureus under AD conditions. AD was induced by injecting capsaicin into neonatal rat pups. ASCs were extracted from the subcutaneous adipose tissues of naïve rats and administered to AD rats once a week for a month. Systemic administration of ASCs ameliorated AD-like symptoms, such as dermatitis scores, serum IgE, IFN-γ+/IL-4+ cell ratio, and skin colonization by S. aureus in AD rats. Increased FasL mRNA and annexin V+/7-AAD+ cells in the PBMCs obtained from AD rats were drastically reversed when co-cultured with ASCs. In contrast, both PBMCs and CD163+ cells bearing fluorescent zymosan particles significantly increased in AD rats treated with ASCs. Additionally, the administration of ASCs led to an increase in the mRNA levels of antimicrobial peptides, such as cathelicidin and β-defensin, in the skin of AD rats. Our results demonstrate that systemic administration of ASCs led to decolonization of S. aureus by attenuating apoptosis of immune cells in addition to restoring phagocytic activity. This contributes to the improvement of skin conditions in AD rats. Therefore, administration of ASCs may be helpful in the treatment of patients with intractable AD.

키워드

과제정보

This research was supported by a grant from Konyang University (2021A0057).

참고문헌

  1. Leung DY, Bieber T. Atopic dermatitis. Lancet. 2003;361:151-160. https://doi.org/10.1016/S0140-6736(03)12193-9
  2. Kasraie S, Werfel T. Role of macrophages in the pathogenesis of atopic dermatitis. Mediators Inflamm. 2013;2013:942375.
  3. Zhang X, Hu X, Rao X. Apoptosis induced by Staphylococcus aureus toxins. Microbiol Res. 2017;205:19-24. https://doi.org/10.1016/j.micres.2017.08.006
  4. Torchinsky MB, Garaude J, Blander JM. Infection and apoptosis as a combined inflammatory trigger. Curr Opin Immunol. 2010;22:55-62. https://doi.org/10.1016/j.coi.2010.01.003
  5. Deng W, Chen W, Zhang Z, Huang S, Kong W, Sun Y, Tang X, Yao G, Feng X, Chen W, Sun L. Mesenchymal stem cells promote CD206 expression and phagocytic activity of macrophages through IL-6 in systemic lupus erythematosus. Clin Immunol. 2015;161:209-216. https://doi.org/10.1016/j.clim.2015.07.011
  6. Poon IK, Lucas CD, Rossi AG, Ravichandran KS. Apoptotic cell clearance: basic biology and therapeutic potential. Nat Rev Immunol. 2014;14:166-180. https://doi.org/10.1038/nri3607
  7. Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, Alfonso ZC, Fraser JK, Benhaim P, Hedrick MH. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell. 2002;13:4279-4295. https://doi.org/10.1091/mbc.E02-02-0105
  8. Valina C, Pinkernell K, Song YH, Bai X, Sadat S, Campeau RJ, Le Jemtel TH, Alt E. Intracoronary administration of autologous adipose tissue-derived stem cells improves left ventricular function, perfusion, and remodelling after acute myocardial infarction. Eur Heart J. 2007;28:2667-2677. https://doi.org/10.1093/eurheartj/ehm426
  9. Harn HJ, Lin SZ, Hung SH, Subeq YM, Li YS, Syu WS, Ding DC, Lee RP, Hsieh DK, Lin PC, Chiou TW. Adipose-derived stem cells can abrogate chemical-induced liver fibrosis and facilitate recovery of liver function. Cell Transplant. 2012;21:2753-2764. https://doi.org/10.3727/096368912X652959
  10. Lee EY, Xia Y, Kim WS, Kim MH, Kim TH, Kim KJ, Park BS, Sung JH. Hypoxia-enhanced wound-healing function of adipose-derived stem cells: increase in stem cell proliferation and up-regulation of VEGF and bFGF. Wound Repair Regen. 2009;17:540-547. https://doi.org/10.1111/j.1524-475X.2009.00499.x
  11. Alexeev V, Arita M, Donahue A, Bonaldo P, Chu ML, Igoucheva O. Human adipose-derived stem cell transplantation as a potential therapy for collagen VI-related congenital muscular dystrophy. Stem Cell Res Ther. 2014;5:21. https://doi.org/10.1186/scrt411
  12. Gonzalez-Rey E, Gonzalez MA, Varela N, O'Valle F, Hernandez-Cortes P, Rico L, Buscher D, Delgado M. Human adipose-derived mesenchymal stem cells reduce inflammatory and T cell responses and induce regulatory T cells in vitro in rheumatoid arthritis. Ann Rheum Dis. 2010;69:241-248. https://doi.org/10.1136/ard.2008.101881
  13. Gonzalez MA, Gonzalez-Rey E, Rico L, Buscher D, Delgado M. Adipose-derived mesenchymal stem cells alleviate experimental colitis by inhibiting inflammatory and autoimmune responses. Gastroenterology. 2009;136:978-989. https://doi.org/10.1053/j.gastro.2008.11.041
  14. Yoon W, Jang S, Kook K. Use of adipose derived stem cells (ASCs) in treating autoimmune skin diseases: pilot study. Cytotherapy. 2016;18(6 Suppl):S132-S133. https://doi.org/10.1016/j.jcyt.2016.03.259
  15. Shin TH, Lee BC, Choi SW, Shin JH, Kang I, Lee JY, Kim JJ, Lee HK, Jung JE, Choi YW, Lee SH, Yoon JS, Choi JS, Lee CS, Seo Y, Kim HS, Kang KS. Human adipose tissue-derived mesenchymal stem cells alleviate atopic dermatitis via regulation of B lymphocyte maturation. Oncotarget. 2017;8:512-522. https://doi.org/10.18632/oncotarget.13473
  16. Back SK, Jeong KY, Li C, Lee J, Lee SB, Na HS. Chronically relapsing pruritic dermatitis in the rats treated as neonate with capsaicin; a potential rat model of human atopic dermatitis. J Dermatol Sci. 2012;67:111-119. https://doi.org/10.1016/j.jdermsci.2012.05.006
  17. Han RT, Kim HY, Ryu H, Jang W, Cha SH, Kim HY, Lee J, Back SK, Kim HJ, Na HS. Glyoxal-induced exacerbation of pruritus and dermatitis is associated with staphylococcus aureus colonization in the skin of a rat model of atopic dermatitis. J Dermatol Sci. 2018;90:276-283. https://doi.org/10.1016/j.jdermsci.2018.02.012
  18. Bunnell BA, Flaat M, Gagliardi C, Patel B, Ripoll C. Adipose-derived stem cells: isolation, expansion and differentiation. Methods. 2008;45:115-120. https://doi.org/10.1016/j.ymeth.2008.03.006
  19. Yardeni T, Eckhaus M, Morris HD, Huizing M, Hoogstraten-Miller S. Retro-orbital injections in mice. Lab Anim (NY). 2011;40:155-160. https://doi.org/10.1038/laban0511-155
  20. Lindner B, Burkard T, Schuler M. Phagocytosis assays with different pH-sensitive fluorescent particles and various readouts. Biotechniques. 2020;68:245-250. https://doi.org/10.2144/btn-2020-0003
  21. Miksa M, Komura H, Wu R, Shah KG, Wang P. A novel method to determine the engulfment of apoptotic cells by macrophages using pHrodo succinimidyl ester. J Immunol Methods. 2009;342:71-77. https://doi.org/10.1016/j.jim.2008.11.019
  22. Lecoeur H, Ledru E, Prevost MC, Gougeon ML. Strategies for phenotyping apoptotic peripheral human lymphocytes comparing ISNT, annexin-V and 7-AAD cytofluorometric staining methods. J Immunol Methods. 1997;209:111-123. https://doi.org/10.1016/S0022-1759(97)00138-5
  23. Kuraitis D, Williams L. Decolonization of Staphylococcus aureus in healthcare: a dermatology perspective. J Healthc Eng. 2018;2018:2382050. https://doi.org/10.1155/2018/2382050
  24. Sohn MH, Kim JW, Kim WK, Jang GC, Kim KE. Staphylococcal enterotoxin B upregulates Fas-mediated apoptosis of peripheral blood mononuclear cells in childhood atopic dermatitis. Scand J Immunol. 2003;57:62-67. https://doi.org/10.1046/j.1365-3083.2003.01183.x
  25. Akdis CA, Akdis M, Trautmann A, Blaser K. Immune regulation in atopic dermatitis. Curr Opin Immunol. 2000;12:641-646. https://doi.org/10.1016/S0952-7915(00)00156-4
  26. Yoshino T, Asada H, Sano S, Nakamura T, Itami S, Tamura M, Yoshikawa K. Impaired responses of peripheral blood mononuclear cells to staphylococcal superantigen in patients with severe atopic dermatitis: a role of T cell apoptosis. J Invest Dermatol. 2000;114:281-288. https://doi.org/10.1046/j.1523-1747.2000.00878.x
  27. Grassme H, Jendrossek V, Gulbins E. Molecular mechanisms of bacteria induced apoptosis. Apoptosis. 2001;6:441-445. https://doi.org/10.1023/A:1012485506972
  28. Bien K, Zmigrodzka M, Orlowski P, Fruba A, Szymanski L, Stankiewicz W, Nowak Z, Malewski T, Krzyzowska M. Involvement of Fas/FasL pathway in the murine model of atopic dermatitis. Inflamm Res. 2017;66:679-690. https://doi.org/10.1007/s00011-017-1049-z
  29. Farley SM, Dotson AD, Purdy DE, Sundholm AJ, Schneider P, Magun BE, Iordanov MS. Fas ligand elicits a caspase-independent proinflammatory response in human keratinocytes: implications for dermatitis. J Invest Dermatol. 2006;126:2438-2451. https://doi.org/10.1038/sj.jid.5700477
  30. Bommhardt U, Chang KC, Swanson PE, Wagner TH, Tinsley KW, Karl IE, Hotchkiss RS. Akt decreases lymphocyte apoptosis and improves survival in sepsis. J Immunol. 2004;172:7583-7591. https://doi.org/10.4049/jimmunol.172.12.7583
  31. Abdullraheem YF, Alzolibani AA, Mahmoud KH, Korsni AH, Al-Harbi MH, Hassanin KM, Al-Dhubaibi MS. Clinical study and assessment of leukocyte phagocytic function in children with atopic dermatitis in Qassim region of Saudi Arabia. Int J Health Sci (Qassim). 2017;11:3-7.
  32. Kim J, Hematti P. Mesenchymal stem cell-educated macrophages: a novel type of alternatively activated macrophages. Exp Hematol. 2009;37:1445-1453. https://doi.org/10.1016/j.exphem.2009.09.004
  33. Porcheray F, Viaud S, Rimaniol AC, Leone C, Samah B, Dereuddre-Bosquet N, Dormont D, Gras G. Macrophage activation switching: an asset for the resolution of inflammation. Clin Exp Immunol. 2005;142:481-489. https://doi.org/10.1111/j.1365-2249.2005.02934.x
  34. Roszer T. Understanding the mysterious M2 macrophage through activation markers and effector mechanisms. Mediators Inflamm. 2015;2015:816460. https://doi.org/10.1155/2015/816460
  35. Yin X, Pang C, Bai L, Zhang Y, Geng L. [Adipose-derived stem cells promote the polarization from M1 macrophages to M2 macrophages]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2016;32:332-338. Chinese.
  36. Han SC, Koo DH, Kang NJ, Yoon WJ, Kang GJ, Kang HK, Yoo ES. Docosahexaenoic acid alleviates atopic dermatitis by generating Tregs and IL-10/TGF-β-modified macrophages via a TGF-β-dependent mechanism. J Invest Dermatol. 2015;135:1556-1564. https://doi.org/10.1038/jid.2014.488
  37. Nguyen LT, Haney EF, Vogel HJ. The expanding scope of antimicrobial peptide structures and their modes of action. Trends Biotechnol. 2011;29:464-472. https://doi.org/10.1016/j.tibtech.2011.05.001
  38. Mallbris L, Carlen L, Wei T, Heilborn J, Nilsson MF, Granath F, Stahle M. Injury downregulates the expression of the human cathelicidin protein hCAP18/LL-37 in atopic dermatitis. Exp Dermatol. 2010;19:442-449. https://doi.org/10.1111/j.1600-0625.2009.00918.x
  39. Nakatsuji T, Gallo RL. The role of the skin microbiome in atopic dermatitis. Ann Allergy Asthma Immunol. 2019;122:263-269. Erratum in: Ann Allergy Asthma Immunol. 2019;123:529. https://doi.org/10.1016/j.anai.2018.12.003
  40. Lee HJ, Jung M, Kim JH, Yoon NY, Choi EH. The effect of adiposederived stem cell-cultured media on oxazolone treated atopic dermatitis-like murine model. Ann Dermatol. 2012;24:181-188. https://doi.org/10.5021/ad.2012.24.2.181
  41. Qian J, Hu Y, Zhao L, Xia J, Li C, Shi L, Xu F. Protective role of adipose-derived stem cells in Staphylococcus aureus-induced lung injury is mediated by RegIIIγ secretion. Stem Cells. 2016;34:1947-1956. Erratum in: Stem Cells. 2016;34:2798. https://doi.org/10.1002/stem.2337
  42. Geoghegan JA, Irvine AD, Foster TJ. Staphylococcus aureus and atopic dermatitis: a complex and evolving relationship. Trends Microbiol. 2018;26:484-497. https://doi.org/10.1016/j.tim.2017.11.008