title: Neoagarohexaose-mediated activation of dendritic cells via Toll-like receptor 4 leads to stimulation of natural killer cells and enhancement of antitumor immunity.
abstract: β-Agarase cleaves the β-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 β-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. [BMB Reports 2017; 50(5): 263-268].
authors.affiliation: Department of Immunology, Laboratory of Dendritic Cell Differentiation and Regulation, School of Medicine, Konkuk University, Chungju 27478, Korea.
authors.forename: Moon Hee
authors.initials: MH
authors.lastname: Lee
authors.affiliation: Department of Dental Hygiene, Hanseo University, Seosan 31962, Korea.
authors.forename: Jong-Hwa
authors.initials: JH
authors.lastname: Jang
authors.affiliation: Department of Immunology, Laboratory of Dendritic Cell Differentiation and Regulation, School of Medicine, Konkuk University, Chungju 27478, Korea.
authors.forename: Gun Young
authors.initials: GY
authors.lastname: Yoon
authors.affiliation: Department of Immunology, Laboratory of Dendritic Cell Differentiation and Regulation, School of Medicine, Konkuk University, Chungju 27478, Korea.
authors.forename: Seung Jun
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Physiology, Korea University, College of Medicine, Seoul 02841, Korea.
authors.forename: Min-Goo
authors.initials: MG
authors.lastname: Lee
authors.affiliation: Department of Immunology, Laboratory of Dendritic Cell Differentiation and Regulation, School of Medicine, Konkuk University, Chungju 27478, Korea.
authors.forename: Tae Heung
authors.initials: TH
authors.lastname: Kang
authors.affiliation: Department of Immunology, Laboratory of Dendritic Cell Differentiation and Regulation, School of Medicine, Konkuk University, Chungju 27478, Korea.
authors.forename: Hee Dong
authors.initials: HD
authors.lastname: Han
authors.affiliation: Department of Immunology, Laboratory of Dendritic Cell Differentiation and Regulation, School of Medicine, Konkuk University, Chungju 27478, Korea.
authors.forename: Hyuk Soon
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Immunology, Laboratory of Dendritic Cell Differentiation and Regulation, School of Medicine, Konkuk University, Chungju 27478, Korea.
authors.forename: Wahn Soo
authors.initials: WS
authors.lastname: Choi
authors.affiliation: Institute of Medical Sciences, Department of Physiology, Kangwon National University School of Medicine, Chuncheon 24341, Korea.
authors.forename: Won Sun
authors.initials: WS
authors.lastname: Park
authors.affiliation: Department of Immunology, Laboratory of Dendritic Cell Differentiation and Regulation, School of Medicine, Konkuk University, Chungju 27478, Korea.
authors.forename: Yeong-Min
authors.initials: YM
authors.lastname: Park
authors.affiliation: Department of Immunology, Laboratory of Dendritic Cell Differentiation and Regulation, School of Medicine, Konkuk University, Chungju 27478, Korea.
authors.forename: In Duk
authors.initials: ID
authors.lastname: Jung
mesh_terms: D000362:Agar / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents; D045744:Cell Line, Tumor / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects*; D006026:Glycoside Hydrolases / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009844:Oligosaccharides / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D009844:Oligosaccharides; D051197:Toll-Like Receptor 4; D007371:Interferon-gamma; D000362:Agar; D006026:Glycoside Hydrolases; C019624:agarase