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新型六糖通过 Toll 样受体 4 激活树突状细胞,进而刺激自然杀伤细胞,增强抗肿瘤免疫。

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

机构信息

Department of Immunology, Laboratory of Dendritic Cell Differentiation and Regulation, School of Medicine, Konkuk University, Chungju 27478, Korea.

Department of Dental Hygiene, Hanseo University, Seosan 31962, Korea.

出版信息

BMB Rep. 2017 May;50(5):263-268. doi: 10.5483/bmbrep.2017.50.5.014.

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].

摘要

β-琼脂酶裂解琼脂的β-1,4 键,产生新琼寡糖(NAO),与各种生理功能有关。然而,NAO 的免疫功能尚不清楚。在这项研究中,我们证明了 β-琼脂酶 DagA 产生的 neoagarohexaose(DP6),一种 NAO 产物,通过 Toll 样受体 4(TLR4)促进树突状细胞(DC)的成熟。DP6 以 TLR4 依赖的方式直接和间接增强体外和体内自然杀伤(NK)细胞的激活。最后,体内使用 NK 细胞耗竭抗体在 NK 细胞耗竭系统中抑制 DP6 对 B16F1 黑素瘤细胞的抗肿瘤活性。总之,这些结果表明 DP6 通过 TLR4 依赖的方式激活 DC 介导的 NK 细胞增强抗肿瘤免疫对 B16F1 黑素瘤细胞的作用。因此,DP6 是一种潜在的候选佐剂,可作为免疫细胞调节剂用于治疗黑色素瘤。[BMB 报告 2017;50(5): 263-268]。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ccd/5458676/0512aa76195a/bmb-50-263f1.jpg

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