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Korean Red Ginseng attenuates ultraviolet-mediated inflammasome activation in keratinocytes

  • Ahn, Huijeong (College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University) ;
  • Han, Byung-Cheol (College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University) ;
  • Hong, Eui-Ju (College of Veterinary Medicine and Institute of Veterinary Science, Chungnam National University) ;
  • An, Beum-Soo (Department of Biomaterial Science, College of Natural Resources and Life Science, Pusan National University) ;
  • Lee, Eunsong (College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University) ;
  • Lee, Seung-Ho (Korea Ginseng Research Institute, Korea Ginseng Corporation) ;
  • Lee, Geun-Shik (College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University)
  • 투고 : 2020.10.13
  • 심사 : 2021.02.09
  • 발행 : 2021.05.01

초록

Background: Keratinocytes form a physical barrier and act as an innate immune cell in skin. Keratinocytes secrete pro-inflammatory cytokines, such as interleukin (IL)-1β, resulting from inflammasome activation when exposed to ultraviolet (UV) irradiation. Korean Red Ginseng extracts (RGE) have been well-studied as modulators of inflammasome activation in immune cells, such as macrophages. In the study, we elucidated the role of RGE on the UV-mediated inflammasome activation in keratinocytes compared with that in macrophages. Methods: Human skin keratinocyte cells (HaCaT), human epidermal keratinocytes (HEK), human monocyte-like cells (THP-1), and mouse macrophages were treated with RGE or a saponin fraction (SF) or non-saponin fraction (NS) of RGE before and after UV irradiation. The secretion levels of IL-1β, as an indicator of inflammasome activation, were analyzed. Results: The treatment of RGE or SF in macrophages after UV irradiation inhibited IL-1β secretion, but similar treatment in HaCaT cells did not. However, the treatment of RGE or SF in HaCaT cells in the presence of poly I:C, a toll-like receptor (TLR) 3 ligand, before UV exposure elicited the inhibition of the IL-1β secretion. The inhibition was caused by the disruption by RGE or SF of the TLR mediating up-regulation of the pro-IL-1β and NLRP3 genes during the priming step. Conclusion: RGE and its saponins inhibit IL-1β secretion in response to UV exposure in both keratinocytes and macrophages. In particular, RGE treatment interrupted only the priming step in keratinocytes, although it did attenuate both the priming and activation steps in macrophages.

키워드

과제정보

This research was supported by a grant (2019) from the Korean Society of Ginseng funded by the Korean Ginseng Corporation and by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (NRF-2018R1A2B2004097 and NRF-2018R1D1A1B07048337).

참고문헌

  1. Nasti TH, Timares L. Inflammasome activation of IL-1 family mediators in response to cutaneous photodamage. Photochemistry and Photobiology 2012;88:1111-25. https://doi.org/10.1111/j.1751-1097.2012.01182.x
  2. Coll RC, Robertson AA, Chae JJ, Higgins SC, Munoz-Planillo R, Inserra MC, Vetter I, Dungan LS, Monks BG, Stutz A, et al. A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases. Nature Medicine 2015;21:248-55. https://doi.org/10.1038/nm.3806
  3. Godar DE, Landry RJ, Lucas AD. Increased UVA exposures and decreased cutaneous Vitamin D(3) levels may be responsible for the increasing incidence of melanoma. Med Hypotheses 2009;72:434-43. https://doi.org/10.1016/j.mehy.2008.09.056
  4. Sand J, Haertel E, Biedermann T, Contassot E, Reichmann E, French LE, Werner S, Beer HD. Expression of inflammasome proteins and inflammasome activation occurs in human, but not in murine keratinocytes. Cell Death & Disease 2018;9:24. https://doi.org/10.1038/s41419-017-0009-4
  5. Ahn H, Kwon HM, Lee E, Kim PH, Jeung EB, Lee GS. Role of inflammasome regulation on immune modulators. J Biomed Res 2018;32:401-10. https://doi.org/10.7555/JBR.32.20170120
  6. Lebre MC, van der Aar AM, van Baarsen L, van Capel TM, Schuitemaker JH, Kapsenberg ML, de Jong EC. Human keratinocytes express functional Toll-like receptor 3, 4, 5, and 9. J Invest Dermatol 2007;127:331-41. https://doi.org/10.1038/sj.jid.5700530
  7. Fan H, Wang Y, Zhang X, Chen J, Zhou Q, Yu Z, Chen Y, Chen Z, Gu J, Shi Y. Ginsenoside compound K ameliorates imiquimod-induced psoriasis-like dermatitis through inhibiting REG3A/RegIIIgamma expression in keratinocytes. Biochem Biophys Res Commun 2019;515:665-71. https://doi.org/10.1016/j.bbrc.2019.06.007
  8. Hou JH, Shin H, Jang KH, Park CK, Koo B, Shin H, Yuk SH, Lee KY. Anti-acne properties of hydrophobic fraction of red ginseng (Panax ginseng C.A. Meyer) and its active components. Phytother Res 2019;33:584-90. https://doi.org/10.1002/ptr.6243
  9. Lee H, Hong Y, Tran Q, Cho H, Kim M, Kim C, Kwon SH, Park S, Park J, Park J. A new role for the ginsenoside RG3 in antiaging via mitochondria function in ultraviolet-irradiated human dermal fibroblasts. Journal of Ginseng Research 2019;43:431-41. https://doi.org/10.1016/j.jgr.2018.07.003
  10. Park JH, Ahn EK, Ko HJ, Lee JY, Hwang SM, Ko S, Oh JS. Korean red ginseng water extract alleviates atopic dermatitis-like inflammatory responses by negative regulation of mitogen-activated protein kinase signaling pathway in vivo. Biomed Pharmacother 2019;117:109066. https://doi.org/10.1016/j.biopha.2019.109066
  11. Park KS, Park DH. The effect of Korean Red Ginseng on full-thickness skin wound healing in rats. Journal of Ginseng Research 2019;43:226-35. https://doi.org/10.1016/j.jgr.2017.12.006
  12. Han BC, Ahn H, Lee J, Jeon E, Seo S, Jang KH, Lee SH, Kim CH, Lee GS. Nonsaponin fractions of Korean Red Ginseng extracts prime activation of NLRP3 inflammasome. Journal of Ginseng Research 2017;41:513-23. https://doi.org/10.1016/j.jgr.2016.10.001
  13. Ahn H, Han BC, Kim J, Kang SG, Kim PH, Jang KH, So SH, Lee SH, Lee GS. Nonsaponin fraction of Korean Red Ginseng attenuates cytokine production via inhibition of TLR4 expression. Journal of Ginseng Research 2019;43:291-9. https://doi.org/10.1016/j.jgr.2018.03.003
  14. Ahn H, Kim J, Kang SG, Yoon SI, Ko HJ, Kim PH, Hong EJ, An BS, Lee E, Lee GS. Mercury and arsenic attenuate canonical and non-canonical NLRP3 inflammasome activation. Sci Rep 2018;8:13659. https://doi.org/10.1038/s41598-018-31717-7
  15. Tang L, Wu W, Fu W, Hu Y. The effects of phototherapy and melanocytes on keratinocytes. Experimental and Therapeutic Medicine 2018;15:3459-66.
  16. Ahn H, Kang SG, Yoon SI, Ko HJ, Kim PH, Hong EJ, An BS, Lee E, Lee GS. Methylene blue inhibits NLRP3, NLRC4, AIM2, and non-canonical inflammasome activation. Scientific Reports 2017;7:12409. https://doi.org/10.1038/s41598-017-12635-6
  17. Lee J, Ahn H, Hong EJ, An BS, Jeung EB, Lee GS. Sulforaphane attenuates activation of NLRP3 and NLRC4 inflammasomes but not AIM2 inflammasome. Cellular Immunology 2016;306-307:53-60. https://doi.org/10.1016/j.cellimm.2016.07.007
  18. Guo H, Callaway JB, Ting JP. Inflammasomes: mechanism of action, role in disease, and therapeutics. Nature Medicine 2015;21:677-87. https://doi.org/10.1038/nm.3893
  19. Mangan MSJ, Olhava EJ, Roush WR, Seidel HM, Glick GD, Latz E. Targeting the NLRP3 inflammasome in inflammatory diseases. Nature Reviews Drug Discovery 2018;17:588-606. https://doi.org/10.1038/nrd.2018.97
  20. Kim J, Ahn H, Han BC, Lee SH, Cho YW, Kim CH, Hong EJ, An BS, Jeung EB, Lee GS. Korean red ginseng extracts inhibit NLRP3 and AIM2 inflammasome activation. Immunology Letters 2014;158:143-50. https://doi.org/10.1016/j.imlet.2013.12.017
  21. Ahn H, Kim J, Jeung EB, Lee GS. Dimethyl sulfoxide inhibits NLRP3 inflammasome activation. Immunobiology 2014;219:315-22. https://doi.org/10.1016/j.imbio.2013.11.003
  22. Lee GS, Subramanian N, Kim AI, Aksentijevich I, Goldbach-Mansky R, Sacks DB, Germain RN, Kastner DL, Chae JJ. The calcium-sensing receptor regulates the NLRP3 inflammasome through Ca2+ and cAMP. Nature 2012;492:123-7. https://doi.org/10.1038/nature11588
  23. Yang Y, Wang H, Kouadir M, Song H, Shi F. Recent advances in the mechanisms of NLRP3 inflammasome activation and its inhibitors. Cell Death & Disease 2019;10:128. https://doi.org/10.1038/s41419-019-1413-8
  24. Olaru F, Jensen LE. Chemokine expression by human keratinocyte cell lines after activation of Toll-like receptors. Experimental Dermatology 2010;19:e314-6. https://doi.org/10.1111/j.1600-0625.2009.01026.x

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