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Neoagarohexaose activates dendritic cells via Toll-like receptor 4, leading to stimulation of natural killer cells and enhancement of antitumor immunity
Moon Hee Lee1, Jong-Hwa Jang2, Gun Young Yun1, Min-Goo Lee3, Tae Heung Kang1, Hee Dong Han1, Seung Jun Lee1, Hyuk Soon Kim1, Wahn Soo Choi1, Yeong-Min Park1,*, Won Sun Park4, In Duk Jung1
1Department of Immunology, Konkuk University,
2Department of Dental Hygiene, Hanseo University,
3Department of Physiology, Korea University,
4Department of Physiology, Kangwon National University
Abstract
b-agarase cleaves b-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 b-agarase DagA-produced neoagarohexaose (DP6), one among the many NAO products, promotes 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. Taken together, the results indicate that DP6 augments antitumor immunity against B16F1 melanoma cells via the activation of DC-mediated NK cell activity in a TLR4-dependent manner. These results suggest that DP6 might be a promising candidate adjuvant that acts as an immune cell modulator for the treatment of melanoma.
Abstract, Accepted Manuscript(in press) [Submitted on February 8, 2017, Accepted on March 9, 2017]
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