Exp Mol Med.  2013 Feb;45(2):e8.

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

Affiliations
  • 1Department of Microbiology and Immunology, School of Medicine, Pusan National University, Yangsan, South Korea. immunpym@pusan.ac.kr
  • 2Division of Malaria and Parasitic Diseases, National Institute of Health, Korea Centers for Disease Control and Prevention, Cheongwon-gun, South Korea.
  • 3Research Center for Hepatic and Biliary Cancer Center, Pusan National University Yangsan Hospital, Yangsan, South Korea.
  • 4Yongsan Hospital College of Medicine, Chung-Ang University, Seoul, South Korea.
  • 5School of Biological Science, University of Ulsan, Ulsan, South Korea.
  • 6Research Institute of Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, South Korea.

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-1beta, tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) 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.

Keyword

adjuvant; dendritic cells; rhamnogalacturonan II; Toll-like receptor 4; tumor

MeSH Terms

Acute-Phase Proteins/metabolism
Adaptor Proteins, Vesicular Transport/metabolism
Animals
Antigens, CD14/metabolism
Bone Marrow Cells/cytology/drug effects
CD8-Positive T-Lymphocytes/*immunology
Carrier Proteins/metabolism
Cell Differentiation/drug effects
Cell Nucleus/drug effects/metabolism
Cell Proliferation/drug effects
Cytokines/biosynthesis
Dendritic Cells/cytology/drug effects/enzymology/*immunology
Enzyme Activation/drug effects
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/*pathology
Pectins/*pharmacology
Phenotype
Protein Transport/drug effects
Receptors, Chemokine/metabolism
Signal Transduction/drug effects
T-Lymphocytes, Cytotoxic/cytology/drug effects
Toll-Like Receptor 4/*agonists/metabolism
Acute-Phase Proteins
Adaptor Proteins, Vesicular Transport
Antigens, CD14
Carrier Proteins
Cytokines
Membrane Glycoproteins
Myeloid Differentiation Factor 88
NF-kappa B
Pectins
Receptors, Chemokine
Toll-Like Receptor 4
Mitogen-Activated Protein Kinases
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