El-Deeb Nehal M, El-Adawi Hala I, El-Wahab Abeer E Abd, Haddad Ahmed M, El Enshasy Hesham A, He You-Wen, Davis Keith R
Biopharmaceutical Product Research Department, Genetic Engineering and Biotechnology Research Institute, City of Scientific Research and Technological Applications (SRTA-CITY), New Borg El-Arab City, Egypt.
Department of Immunology, Duke University Medical Center, Durham, NC, United States.
Front Cell Dev Biol. 2019 Aug 13;7:165. doi: 10.3389/fcell.2019.00165. eCollection 2019.
Medicinal mushrooms have been used for centuries against cancer and infectious diseases. These positive biological effects of mushrooms are due in part to the indirect action of stimulating immune cells. The objective of the current study is to investigate the possible immunomodulatory effects of mushroom polysaccharides on NK cells against different cancer cells. In this current study, fruiting bodies isolated from cultured were extracted and partially purified using DEAE ion-exchange chromatography. The activation action of the collected fractions on Natural Killer cells was quantified against three different cancer cell lines in the presence or absence of human recombinant IL2 using three different activation and co-culture conditions. The possible modes of action of mushroom polysaccharides against cancer cells were evaluated at the cellular and molecular levels. Our results indicate that polysaccharides induced NK-cells cytotoxic effects against lung and breast cancer cells with the largest effect being against breast cancer cells (81.2%). NK cells activation for cytokine secretion was associated with upregulation of KIR2DL genes while the cytotoxic activation effect of NK cells against cancer cells correlated with NKG2D upregulation and induction of IFNγ and NO production. These cytotoxic effects were enhanced in the presence of IL2. Analysis of the most active partially purified fraction indicates that it is predominantly composed of glucans. These results indicate bioactive 6-linked glucans present in extracts activate NK-cell cytotoxicity via regulation of activation and induction of IFNγ and NO. These studies establish a positive role for bioactive polysaccharides in NK-cells activation and induction of an innate immune response against breast and lung cancer cells.
药用蘑菇已被用于对抗癌症和传染病达数百年之久。蘑菇的这些积极生物学效应部分归因于刺激免疫细胞的间接作用。本研究的目的是调查蘑菇多糖对NK细胞针对不同癌细胞的可能免疫调节作用。在本研究中，从培养物中分离出的子实体经提取后，使用DEAE离子交换色谱法进行部分纯化。在存在或不存在人重组IL2的情况下，使用三种不同的激活和共培养条件，针对三种不同的癌细胞系对收集的级分对自然杀伤细胞的激活作用进行定量。在细胞和分子水平上评估了蘑菇多糖对癌细胞的可能作用模式。我们的结果表明，[蘑菇名称]多糖诱导NK细胞对肺癌和乳腺癌细胞产生细胞毒性作用，其中对乳腺癌细胞的作用最大（81.2%）。NK细胞激活以分泌细胞因子与KIR2DL基因上调相关，而NK细胞对癌细胞的细胞毒性激活作用与NKG2D上调以及IFNγ和NO产生的诱导相关。在IL2存在的情况下，这些细胞毒性作用增强。对活性最高的部分纯化级分的分析表明，它主要由葡聚糖组成。这些结果表明，[蘑菇名称]提取物中存在的具有生物活性的6-连接葡聚糖通过调节激活以及诱导IFNγ和NO来激活NK细胞的细胞毒性。这些研究确立了生物活性[蘑菇名称]多糖在NK细胞激活以及诱导针对乳腺癌和肺癌细胞的先天免疫反应中的积极作用。
