Modulation of NKG2D, KIR2DL and Cytokine Production by Pleurotus ostreatus Glucan Enhances Natural Killer Cell Cytotoxicity Toward Cancer Cells

Frontiers in Cell and Developmental Biology

卷:7

Nehal M. EL-Deeb²  Keith R. Davis²  Hesham A. EL Enshasy³  You-Wen He⁴  Ahmed M. Haddad⁵  Hala I. EL-Adawi⁷  Abeer E. Abd EL-wahab⁷ 

[1] 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;

[2] Department of Biology and Biotechnology Program, Indiana University, Bloomington, IN, United States;

[3] Department of Bioprocess Engineering, Faculty of Chemical and Energy Engineering, Universiti Teknologi Malaysia, Johor Bahru, Malaysia;

[4] Department of Immunology, Duke University Medical Center, Durham, NC, United States;

[5] Environmental Biotechnology Department, Genetic Engineering and Biotechnology Research Institute, City of Scientific Research and Technological Applications (SRTA-CITY), New Borg El-Arab City, Egypt;

[6] Institute of Bioproduct Development, Universiti Teknologi Malaysia, Johor Bahru, Malaysia;

[7] Medical Biotechnology Department, Genetic Engineering and Biotechnology Research Institute, City of Scientific Research and Technological Applications (SRTA-CITY), New Borg El-Arab City, Egypt;

关键词: NK cells;    mushroom;    Pleurotus ostreatus;    breast cancer;    lung cancer;    polysaccharides;   

DOI  :  10.3389/fcell.2019.00165

来源: DOAJ

【 摘 要 】

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 Pleurotus ostreatus 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 P. ostreatus 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 P. ostreatus extracts activate NK-cell cytotoxicity via regulation of activation and induction of IFNγ and NO. These studies establish a positive role for bioactive P. ostreatus polysaccharides in NK-cells activation and induction of an innate immune response against breast and lung cancer cells.

【 授权许可】

Unknown