Cordlan polysaccharide isolated from mushroom Cordyceps militaris induces dendritic cell maturation through toll-like receptor 4 signalings.
Defect of dendritic cell (DC) maturation in tumor microenvironments is an important immunological problem limiting the success of cancer immunotherapy. Here, we investigated the effects of polysaccharide (cordlan) isolated from Cordyceps militaris on DC maturation. Phenotypic maturation of DCs by cordlan was demonstrated by the elevated expressions of CD40, CD80, CD86, MHC-I, and MHC-II molecules, and functional maturation by increased expression of IL-12, IL-1beta, TNF-alpha, and IFN-alphabeta, enhanced allogenic T cell stimulation, and decreased endocytosis. Of note was that cordlan induced maturation of tlr4+/+ DCs from C3H/HeN mice, but not tlr4(-/-) DCs from C3H/HeJ mice, suggesting the promising membrane receptor of cordlan. In addition, cordlan increased phosphorylation of ERK, p38, and JNK, and nuclear translocation of NF-kappaB p50/p65, which were main signaling molecules down-stream from TLR4. These results indicate that cordlan induces DC maturation through TLR4 signaling pathways.
Kim
Hyung Sook
HS
College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 361-763, South Korea.
Kim
Jee Youn
JY
Kang
Jong Soon
JS
Kim
Hwan Mook
HM
Kim
Yong Ook
YO
Hong
In Pyo
IP
Lee
Mi Kyeong
MK
Hong
Jin Tae
JT
Kim
Youngsoo
Y
Han
Sang-Bae
SB
D000818:Animals; D015153:Blotting, Western; D002469:Cell Separation; D032661:Cordyceps / Q000737:chemistry*; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects*; D004705:Endocytosis / Q000187:drug effects; D005260:Female; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D052002:NF-kappa B p50 Subunit / Q000378:metabolism; D011134:Polysaccharides / Q000737:chemistry / Q000494:pharmacology*; D021381:Protein Transport / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000187:drug effects*; D051996:Transcription Factor RelA / Q000378:metabolism
D016207:Cytokines; D052002:NF-kappa B p50 Subunit; D011134:Polysaccharides; D051197:Toll-Like Receptor 4; D051996:Transcription Factor RelA; D020928:Mitogen-Activated Protein Kinases