Neoagarohexaose-mediated activation of dendritic cells via Toll-like receptor 4 leads to stimulation of natural killer cells and enhancement of antitumor immunity

• Published in: BMB reports Vol. 50; no. 5; pp. 263 - 268
• Main Authors: Lee, Moon Hee, Jang, Jong-Hwa, Yoon, Gun Young, Lee, Seung Jun, Lee, Min-Goo, Kang, Tae Heung, Han, Hee Dong, Kim, Hyuk Soon, Choi, Wahn Soo, Park, Won Sun, Park, Yeong-Min, Jung, In Duk
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Society for Biochemistry and Molecular Biology 01.05.2017; 생화학분자생물학회
• Subjects: Agar - chemistry; Agar - pharmacology; Animals; Antineoplastic Agents; Cell Line, Tumor - drug effects; Dendritic Cells - cytology; Dendritic Cells - drug effects; Glycoside Hydrolases - metabolism; Interferon-gamma - metabolism; Killer Cells, Natural - drug effects; Killer Cells, Natural - physiology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Oligosaccharides - immunology; Oligosaccharides - metabolism; Oligosaccharides - pharmacology; Toll-Like Receptor 4 - metabolism; 화학
• ISSN: 1976-6696; 1976-670X
• DOI: 10.5483/BMBRep.2017.50.5.014

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].