Open AccessGSP-2, a polysaccharide extracted from Ganoderma sinense, is a novel toll-like receptor 4 agonist
Author(s) -
Kaisheng Liu,
Cheng Zhang,
Han Dong,
Kai-Kai Li,
QuanBin Han,
Yong Wan,
Rui Chen,
Fang Yang,
Haili Li,
ChunHay Ko,
Xiaoqiang Han
Publication year - 2019
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0221636
Subject(s) - tlr4 , toll like receptor , immune system , receptor , tlr2 , biology , signal transduction , tumor necrosis factor alpha , mapk/erk pathway , microbiology and biotechnology , pattern recognition receptor , secretion , cytokine , ganoderma , proinflammatory cytokine , innate immune system , inflammation , immunology , biochemistry , ganoderma lucidum , food science
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 overexpressing 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 TNFα 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 TNFα, IL1β, and IL6. Our data demonstrated that GSP-2 was specifically recognized by TLR4, promoting cytokine secretion and immune modulation in macrophages.