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

Exp Mol Med. 2013 Feb 8;45(2):e8. doi: 10.1038/emm.2013.14.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins / metabolism
  • Adaptor Proteins, Vesicular Transport / metabolism
  • Animals
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / drug effects
  • CD8-Positive T-Lymphocytes / immunology*
  • Carrier Proteins / metabolism
  • Cell Differentiation / drug effects
  • Cell Nucleus / drug effects
  • Cell Nucleus / metabolism
  • Cell Proliferation / drug effects
  • Cytokines / biosynthesis
  • Dendritic Cells / cytology
  • Dendritic Cells / drug effects
  • Dendritic Cells / enzymology
  • Dendritic Cells / immunology*
  • Enzyme Activation / drug effects
  • Lipopolysaccharide Receptors / metabolism
  • Lymphocyte Activation / drug effects*
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitogen-Activated Protein Kinases / metabolism
  • Myeloid Differentiation Factor 88 / metabolism
  • NF-kappa B / metabolism
  • Neoplasms / immunology
  • Neoplasms / pathology*
  • Pectins / pharmacology*
  • Phenotype
  • Protein Transport / drug effects
  • Receptors, Chemokine / metabolism
  • Signal Transduction / drug effects
  • T-Lymphocytes, Cytotoxic / cytology
  • T-Lymphocytes, Cytotoxic / drug effects
  • Toll-Like Receptor 4 / agonists*
  • Toll-Like Receptor 4 / metabolism

Substances

  • Acute-Phase Proteins
  • Adaptor Proteins, Vesicular Transport
  • Carrier Proteins
  • Cytokines
  • Lipopolysaccharide Receptors
  • Membrane Glycoproteins
  • Myeloid Differentiation Factor 88
  • NF-kappa B
  • Receptors, Chemokine
  • TICAM-1 protein, mouse
  • Toll-Like Receptor 4
  • lipopolysaccharide-binding protein
  • rhamnogalacturonan II
  • Pectins
  • Mitogen-Activated Protein Kinases