Angelan isolated from Angelica gigas Nakai induces dendritic cell maturation through toll-like receptor 4.
During the evolution of neoplastic diseases, dendritic cell (DC) functions are usually attenuated, and this presents a problem to DC-based immunotherapies against cancer. Here, we investigated the effects of angelan, an acidic polysaccharide isolated from Angelica gigas Nakai, on DC maturation. Angelan efficiently increased the maturation of tlr4(+/+) DCs from C57BL/6 and C3H/HeN mice, but not tlr4(-/-) DCs from C3H/HeJ mice. Phenotypic maturation was confirmed by the elevated expressions of CD80, CD86, and MHC-class II molecules, and functional maturation by increased IL-12 production, enhanced allogenic T cell stimulation, and decreased endocytosis. Angelan was found to activate ERK and NF-kappaB, which are signaling molecules down-stream of toll-like receptor-4 (TLR4) receptors. Angelan-treated mature DC more effectively inhibited B16F10 tumor growth than immature DCs in syngenic murine tumor model. These results indicate that angelan induces DC maturation via TLR4 signaling pathways and suggest the possible use of angelan in DC-based immunotherapies.
Kim
Jee Youn
JY
Bioevaluation center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 52 Oundong, Yusong, Daejon 305-806, Korea.
Yoon
Yeo Dae
YD
Ahn
Ji Mi
JM
Kang
Jong Soon
JS
Park
Song-Kyu
SK
Lee
Kiho
K
Song
Kyung Bin
KB
Kim
Hwan Mook
HM
Han
Sang-Bae
SB
D029969:Angelica / Q000737:chemistry; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D004705:Endocytosis / Q000187:drug effects; D005260:Female; D007959:Lymphocyte Culture Test, Mixed; D008546:Melanoma, Experimental / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D011134:Polysaccharides / Q000302:isolation & purification / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000276:immunology*; D023041:Xenograft Model Antitumor Assays
D016207:Cytokines; D011134:Polysaccharides; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; C515883:angelan