TY - JOUR
T1 - GSP-2, a polysaccharide extracted from Ganoderma sinense, is a novel toll-like receptor 4 agonist
AU - Liu, Kai Sheng
AU - Zhang, Cheng
AU - Dong, Hong Liang
AU - Li, Kai Kai
AU - Han, Quan Bin
AU - Wan, Yong
AU - Chen, Rui
AU - Yang, Fang
AU - Li, Hai Li
AU - Ko, Chun Hay
AU - Han, Xiao Qiang
N1 - Funding Information:
This work was funded by the National Natural Science Foundation of China (NO. 81802749, NO. 81303210), the Cultivating Fund Project of Shenzhen People's Hospital (SYKYPY201928), and the Science and Technology Foundation of Shenzhen (JCYJ20180301170047864). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher copyright:
© 2019 Liu et al.
PY - 2019/8/23
Y1 - 2019/8/23
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85071329690&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0221636
DO - 10.1371/journal.pone.0221636
M3 - Journal article
C2 - 31442262
AN - SCOPUS:85071329690
SN - 1932-6203
VL - 14
JO - PLoS ONE
JF - PLoS ONE
IS - 8
M1 - e0221636
ER -
