| First Author | Liu KS | Year | 2019 |
| Journal | PLoS One | Volume | 14 |
| Issue | 8 | Pages | e0221636 |
| PubMed ID | 31442262 | Mgi Jnum | J:279138 |
| Mgi Id | MGI:6359326 | Doi | 10.1371/journal.pone.0221636 |
| Citation | Liu KS, et al. (2019) GSP-2, a polysaccharide extracted from Ganoderma sinense, is a novel toll-like receptor 4 agonist. PLoS One 14(8):e0221636 |
| abstractText | 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 TNFalpha 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 TNFalpha, IL1beta, and IL6. Our data demonstrated that GSP-2 was specifically recognized by TLR4, promoting cytokine secretion and immune modulation in macrophages. |
