机构：[1]The First Affiliated Hospital of Southern University of Science and Technology, The Second Clinical Medical College of Jinan University, Shenzhen People’s Hospital, Shenzhen, Guangdong, China深圳市人民医院深圳医学信息中心[2]Institute of Chinese Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China[3]Institute of Biology and Medical Sciences, Soochow University, Suzhou, Jiangsu, China[4]College of Food Science and Technology, Huazhong Agricultural University, Wuhan, Hubei, China[5]School of Chinese Medicine, Hong Kong Baptist University, Kowloon, Hong Kong SAR, China[6]Shenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, Guangdong, China
Ganoderma sinense is a Chinese unique medicinal fungus that has been used in folk medicine for thousands of years. Polysaccharides are considered to be biologically active ingredients due to their immune-modulating functions. Previously we found that GSP-2, a new polysaccharide isolated from Ganoderma sinense, exerts an immunomodulatory effect in human peripheral blood mononuclear cells but the underlying mechanism is unclear. The present study aimed to investigate how GSP-2 triggers immunologic responses and the implicated signaling pathways. GSP-2 effects were investigated both in a macrophagic cell line, RAW264.7, and in primary macrophages. Moreover, the molecular basis of GSP-2 recognition by immune cells, and the consequent activation of signaling cascades, were explored by employing recombinant human HEK293-TLR-Blue clones, individually over-expressing various Toll-like receptors. GSP-2 dose-dependently induced the overexpression of Toll-like receptor 4 (TLR4) but did not affect the expression of other TLRs. Moreover, GSP-2 induced TNF alpha secretion in primary macrophages from wild-type, but not TLR4-knockout mice. In addition, GSP-2 upregulated TLR4 protein expression and activated the MAPK pathway in RAW246.7 macrophages. Finally, GSP-2 induced the production of the cytokines TNF alpha, IL1 beta, and IL6. Our data demonstrated that GSP-2 was specifically recognized by TLR4, promoting cytokine secretion and immune modulation in macrophages.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81802749, 81303210]; Cultivating Fund Project of Shenzhen People's Hospital [SYKYPY201928]; Science and Technology Foundation of Shenzhen [JCYJ20180301170047864]
第一作者机构：[1]The First Affiliated Hospital of Southern University of Science and Technology, The Second Clinical Medical College of Jinan University, Shenzhen People’s Hospital, Shenzhen, Guangdong, China
通讯作者：
推荐引用方式(GB/T 7714)：
Kai-Sheng Liu,Cheng Zhang,Hong-Liang Dong,et al.GSP-2, a polysaccharide extracted from Ganoderma sinense, is a novel toll-like receptor 4 agonist[J].PLOS ONE.2019,14(8):doi:10.1371/journal.pone.0221636.
APA：
Kai-Sheng Liu,Cheng Zhang,Hong-Liang Dong,Kai-Kai Li,Quan-Bin Han...&Xiao-Qiang Han.(2019).GSP-2, a polysaccharide extracted from Ganoderma sinense, is a novel toll-like receptor 4 agonist.PLOS ONE,14,(8)
MLA：
Kai-Sheng Liu,et al."GSP-2, a polysaccharide extracted from Ganoderma sinense, is a novel toll-like receptor 4 agonist".PLOS ONE 14..8(2019)
