title: Immunomodulatory properties of medicinal mushrooms: differential effects of water and ethanol extracts on NK cell-mediated cytotoxicity.
abstract: Medicinal mushrooms have been used for centuries in Asian countries owing to their beneficial effects on health and longevity. Previous studies have reported that a single medicinal mushroom may produce both stimulatory and inhibitory effects on immune cells, depending on conditions, but the factors responsible for this apparent dichotomy remain obscure. We show here that water and ethanol extracts of cultured mycelium from various species (Agaricus blazei Murrill, Antrodia cinnamomea, Ganoderma lucidum and Hirsutella sinensis) produce opposite effects on NK cells. Water extracts enhance NK cell cytotoxic activity against cancer cells, whereas ethanol extracts inhibit cytotoxicity. Water extracts stimulate the expression and production of cytolytic proteins (perforin and granulysin) and NKG2D/NCR cell surface receptors, and activate intracellular signaling kinases (ERK, JNK and p38). In contrast, ethanol extracts inhibit expression of cytolytic and cell surface receptors. Our results suggest that the mode of extraction of medicinal mushrooms may determine the nature of the immunomodulatory effects produced on immune cells, presumably owing to the differential solubility of stimulatory and inhibitory mediators. These findings have important implications for the preparation of medicinal mushrooms to prevent and treat human diseases.
authors.affiliation: Department of Respiratory Therapy, Fu Jen Catholic University, New Taipei City, Taiwan, Republic of China.
authors.forename: Chia-Chen
authors.initials: CC
authors.lastname: Lu
authors.affiliation: Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China.
authors.forename: Ya-Jing
authors.initials: YJ
authors.lastname: Hsu
authors.affiliation: Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China Center for Molecular and Clinical Immunology, Chang Gung University, Taoyuan, Taiwan, Republic of China Research Center of Bacterial Pathogenesis, Chang Gung University, Taoyuan, Taiwan, Republic of China Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China.
authors.forename: Chih-Jung
authors.initials: CJ
authors.lastname: Chang
authors.affiliation: Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China Center for Molecular and Clinical Immunology, Chang Gung University, Taoyuan, Taiwan, Republic of China Research Center of Bacterial Pathogenesis, Chang Gung University, Taoyuan, Taiwan, Republic of China Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China.
authors.forename: Chuan-Sheng
authors.initials: CS
authors.lastname: Lin
authors.affiliation: Center for Molecular and Clinical Immunology, Chang Gung University, Taoyuan, Taiwan, Republic of China Laboratory of Nanomaterials, Chang Gung University, Taoyuan, Taiwan, Republic of China.
authors.forename: Jan
authors.initials: J
authors.lastname: Martel
authors.affiliation: Center for Molecular and Clinical Immunology, Chang Gung University, Taoyuan, Taiwan, Republic of China Department of Biomedical Sciences, University of the Pacific, Arthur Dugoni School of Dentistry, San Francisco, CA, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Ojcius
authors.affiliation: Chang Gung Biotechnology Corporation, Taipei, Taiwan, Republic of China Biochemical Engineering Research Center, Ming Chi University of Technology, New Taipei City, Taiwan, Republic of China.
authors.forename: Yun-Fei
authors.initials: YF
authors.lastname: Ko
authors.affiliation: Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China Center for Molecular and Clinical Immunology, Chang Gung University, Taoyuan, Taiwan, Republic of China Research Center of Bacterial Pathogenesis, Chang Gung University, Taoyuan, Taiwan, Republic of China Department of Microbiology and Immunology, College of Medicine, Chang Gung University, Taoyuan, Taiwan, Republic of China Department of Laboratory Medicine, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan, Republic of China Research Center for Industry of Human Ecology, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan, Republic of China Graduate Institute of Health Industry and Technology, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan, Republic of China hclai@mail.cgu.edu.tw dingeyoung@hotmail.com.
authors.forename: Hsin-Chih
authors.initials: HC
authors.lastname: Lai
authors.affiliation: Center for Molecular and Clinical Immunology, Chang Gung University, Taoyuan, Taiwan, Republic of China Laboratory of Nanomaterials, Chang Gung University, Taoyuan, Taiwan, Republic of China Chang Gung Biotechnology Corporation, Taipei, Taiwan, Republic of China Biochemical Engineering Research Center, Ming Chi University of Technology, New Taipei City, Taiwan, Republic of China Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, NY, USA hclai@mail.cgu.edu.tw dingeyoung@hotmail.com.
authors.forename: John D
authors.initials: JD
authors.lastname: Young
mesh_terms: D000363:Agaricales / Q000276:immunology*; D000818:Animals; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D000431:Ethanol / Q000737:chemistry; D006801:Humans; D056747:Immunomodulation; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D008518:Medicine, East Asian Traditional; D025282:Mycelium; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D054353:Perforin / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D015398:Signal Transduction; D014867:Water / Q000737:chemistry; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C527085:KLRK1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K; D010936:Plant Extracts; D014867:Water; D054353:Perforin; D000431:Ethanol; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Agaricus blazei Murrill; Antrodia cinnamomea; Ganoderma lucidum; Hirsutella sinensis; Ophiocordyceps sinensis; caterpillar fungus; extraction; immunomodulatory effects; innate immunity; medicinal mushrooms