A triterpenoid methyl antcinate K isolated from Antrodia cinnamomea promotes dendritic cell activation and Th2 differentiation.
Dendritic cells (DC) play a central role in the initiation and regulation of immune responses. Increasing evidence has indicated that manipulation of DC can serve as a therapeutic mechanism for immunomodulation. In this study we tested some unique compounds isolated from Antrodia cinnamomea, a medicinal fungus in Taiwan, on mouse bone marrow-derived DC activation. A triterpenoid methyl antcinate K (me-AntK) promoted DC maturation by enhancing the expression of MHC class II, CD86, and reducing the endocytosis. TNF-alpha, MCP-1, and MIP-1beta were secreted by DC after me-AntK treatment, indicating augmentation of innate immunity by me-AntK. Interestingly, the me-AntK-activated DC induced Ag-specific T-cell proliferation and facilitated Th2 differentiation. Examining signaling responses, we found that me-AntK treatment uniquely activated JNK and ERK in DC. Our results demonstrate that me-AntK is the first natural triterpenoid to promote the ability of DC to prime Th2 responses. This suggests that me-AntK can potentially be applied to enhance immune responses and modulate DC function in immunotherapy.
Yu
Yen-Ling
YL
Vaccine Research and Development Center, National Health Research Institutes, Miaoli, Taiwan.
Chen
I-Hua
IH
Shen
Kuan-Yin
KY
Huang
Ren-Yeong
RY
Wang
Wu-Rong
WR
Chou
Cheng-Jen
CJ
Chang
Tun-Tschu
TT
Chu
Ching-Liang
CL
D000818:Animals; D055491:Antrodia / Q000737:chemistry*; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007074:Immunoglobulin G / Q000097:blood; D007155:Immunologic Factors / Q000302:isolation & purification / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology; D014315:Triterpenes / Q000302:isolation & purification / Q000494:pharmacology*
D016207:Cytokines; D007074:Immunoglobulin G; D007155:Immunologic Factors; D014315:Triterpenes; C543695:methyl antcinate K; D010047:Ovalbumin; D048049:Extracellular Signal-Regulated MAP Kinases; D048670:MAP Kinase Kinase 4