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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Neoagarohexaose-mediated activation of dendritic cells via Toll-like receptor 4 leads to stimulation of natural killer cells and enhancement of antitumor immunity

  • Lee, Moon Hee (Department of Immunology, Laboratory of Dendritic Cell Differentiation and Regulation, School of Medicine, Konkuk University) ;
  • Jang, Jong-Hwa (Department of Dental Hygiene, Hanseo University) ;
  • Yoon, Gun Young (Department of Immunology, Laboratory of Dendritic Cell Differentiation and Regulation, School of Medicine, Konkuk University) ;
  • Lee, Seung Jun (Department of Immunology, Laboratory of Dendritic Cell Differentiation and Regulation, School of Medicine, Konkuk University) ;
  • Lee, Min-Goo (Department of Physiology, Korea University, College of Medicine) ;
  • Kang, Tae Heung (Department of Immunology, Laboratory of Dendritic Cell Differentiation and Regulation, School of Medicine, Konkuk University) ;
  • Han, Hee Dong (Department of Immunology, Laboratory of Dendritic Cell Differentiation and Regulation, School of Medicine, Konkuk University) ;
  • Kim, Hyuk Soon (Department of Immunology, Laboratory of Dendritic Cell Differentiation and Regulation, School of Medicine, Konkuk University) ;
  • Choi, Wahn Soo (Department of Immunology, Laboratory of Dendritic Cell Differentiation and Regulation, School of Medicine, Konkuk University) ;
  • Park, Won Sun (Institute of Medical Sciences, Department of Physiology, Kangwon National University School of Medicine) ;
  • Park, Yeong-Min (Department of Immunology, Laboratory of Dendritic Cell Differentiation and Regulation, School of Medicine, Konkuk University) ;
  • Jung, In Duk (Department of Immunology, Laboratory of Dendritic Cell Differentiation and Regulation, School of Medicine, Konkuk University)
  • Received : 2017.02.08
  • Accepted : 2017.03.09
  • Published : 2017.05.31
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Abstract

${\beta}$-Agarase cleaves the ${\beta}$-1,4 linkages of agar to produce neoagarooligosaccharides (NAO), which are associated with various physiological functions. However, the immunological functions of NAO are still unclear. In this study, we demonstrated that ${\beta}$-agarase DagA-produced neoagarohexaose (DP6), an NAO product, promoted the maturation of dendritic cells (DCs) by Toll-like receptor 4 (TLR4). DP6 directly and indirectly enhanced the activation of natural killer (NK) cells in a TLR4-dependent manner in vitro and in vivo. Finally, the antitumor activity of DP6 against B16F1 melanoma cells was inhibited in NK cell-depletion systems by using NK-cell depleting antibodies in vivo. Collectively, the results indicated that DP6 augments antitumor immunity against B16F1 melanoma cells via the activation of DC-mediated NK cells in a TLR4-dependent manner. Thus, DP6 is a potential candidate adjuvant that acts as an immune cell modulator for the treatment of melanoma.

Keywords

References

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