Rhamnogalacturonan II is a Toll-like receptor 4 agonist that inhibits tumor growth by activating dendritic cell-mediated CD8+ T cells

Abstract

We evaluated the effectiveness of rhamnogalacturonan II (RG-II)-stimulated bone marrow-derived dendritic cells (BMDCs) vaccination on the induction of antitumor immunity in a mouse lymphoma model using EG7-lymphoma cells expressing ovalbumin (OVA). BMDCs treated with RG-II had an activated phenotype. RG-II induced interleukin (IL)-12, IL-1β, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) production during dendritic cell (DC) maturation. BMDCs stimulated with RG-II facilitate the proliferation of CD8+ T cells. Using BMDCs from the mice deficient in Toll-like receptors (TLRs), we revealed that RG-II activity is dependent on TLR4. RG-II showed a preventive effect of immunization with OVA-pulsed BMDCs against EG7 lymphoma. These results suggested that RG-II expedites the DC-based immune response through the TLR4 signaling pathway.

Fruit-Derived Polysaccharides and Terpenoids: Recent Update on the Gastroprotective Effects and Mechanisms

“…Further findings from the in vivo study using transgenic mouse model supported the notion that the RG could have activated DC through Toll like receptor 4 , resulting in phenotypic maturation of DC and activation of mitogen-activated protein kinase (MAPK) signal pathway. The study also demonstrated successful targeting and ultimately, inhibition of EG7 lymphoma cell growth ( Park et al, 2013 ). Therefore, it is worthy for us to explore into the feasibility to use RG as a natural drug product to prevent gastric cancer formation as a result of H. pylori infection, and study the possible mechanisms involved in the suppression of gastric cancer cells before advancement to later stages.…”

“…However, RG seems capable of eliciting sufficient immune responses to eradicate tumor cells. For instance, in a study conducted by Park et al (2013) , a ramified form of RG (RG-2) extracts from Panax ginseng were able to enhance antigen presentation and stimulatory capability of dendritic cells to CD8+ T-lymphocytes after priming with ovalbumin-expressing EL-4 (EG7) tumor cells. Further findings from the in vivo study using transgenic mouse model supported the notion that the RG could have activated DC through Toll like receptor 4 , resulting in phenotypic maturation of DC and activation of mitogen-activated protein kinase (MAPK) signal pathway.…”

Antioxidant and antimicrobial activities of a purified polysaccharide from yerba mate (Ilex paraguariensis)

“…For example, a RG-II-type polysaccharide isolated from mature leaves of green tea, presented antitumor and anti-metastatic activities via activation of macrophages and natural killer cells [52]. RG-II isolated from the leaves of Panax ginseng inhibited tumor growth by activating dendritic cell-mediated CD8 + T cells [53]. Furthermore, a RG-I domain-rich pectin from potato inhibited the proliferation of HT-29 cells and induced significant G2/M cell cycle arrest [54].…”

Harnessing the Induction of CD8+ T-Cell Responses Through Metabolic Regulation by Pathogen-Recognition-Receptor Triggering in Antigen Presenting Cells

“…The canonical Toll-like receptor 4 (TLR4) signaling cascade is initiated when lipid A (the membrane anchor of lipopolysaccharide [LPS]) is bound by the extracellular region of CD14, which complexes with MD2 and binds to membrane-bound TLR4 ( 46 ). Dimerization of these molecules with another lipid A-MD2-TLR4 complex creates a functional TLR4 signaling complex ( 47 ). Binding of a TLR4 agonist like lipid A initiates an innate immune response that can drive the development of antigen-specific acquired immunity ( 48 ).…”