title: Ursolic acid isolated from Uncaria rhynchophylla activates human dendritic cells via TLR2 and/or TLR4 and induces the production of IFN-gamma by CD4+ naïve T cells.
abstract: Ursolic acid is triterpene isolated from Uncaria rhynchophylla and is a pharmacologically active substance. The induction of dendritic cell maturation is critical for the induction of Ag-specific T-lymphocyte response and may be essential for the development of human vaccine relying on T cell immunity. In this study, we investigated that the effect of Ursolic acid on the phenotypic and functional maturation of human monocyte-derived dendritic cells in vitro. Dendritic cells harvested on day 8 were examined using functional assay. The expression levels of CD1a, CD80, CD83, CD86, HLA-DR and CCR7 on Ursolic acid-primed dendritic cells was slightly enhanced. Ursolic acid dose-dependently enhanced the T cell stimulatory capacity in an allogeneic mixed lymphocyte reaction, as measured by T cell proliferation. The production of IL-12p70 induced by Ursolic acid-primed dendritic cells was inhibited by the anti-Toll-like receptor-2 (TLR2) mAb and anti-TLR4 mAb. Moreover, Ursolic acid-primed dendritic cells expressed levels of mRNA coding for both TLR2 and TLR4. The majority of cells produced considerable interferon-gamma (IFN-gamma), but also small amounts of interleukin (IL-4)-4. Ursolic acid-primed dendritic cells have an intermediate migratory capacity towards CCL19 and CCL21. These results suggest that Ursolic acid modulates human dendritic cells function in a fashion that favors Th1 polarization via the activation of IL-12p70 dependent on TLR2 and/or TLR4, and may be used on dendritic cells-based vaccines for cancer immunotherapy.
authors.affiliation: Department of Neurosurgery, Chonnam National University Medical School, Gwangiu, South Korea.
authors.forename: Tae-Young
authors.initials: TY
authors.lastname: Jung
authors.forename: Thanh Nhan Nguyen
authors.initials: TN
authors.lastname: Pham
authors.forename: Akemi
authors.initials: A
authors.lastname: Umeyama
authors.forename: Noboru
authors.initials: N
authors.lastname: Shoji
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Hashimoto
authors.forename: Je-Jung
authors.initials: JJ
authors.lastname: Lee
authors.forename: Masao
authors.initials: M
authors.lastname: Takei
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D019742:Chemokines, CC / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology*; D004365:Drugs, Chinese Herbal / Q000737:chemistry; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000378:metabolism*; D007378:Interleukins / Q000378:metabolism; D009994:Osmolar Concentration; D012333:RNA, Messenger / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014315:Triterpenes / Q000494:pharmacology*; D032070:Uncaria / Q000737:chemistry; D000097245:Ursolic Acid
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D019742:Chemokines, CC; D004365:Drugs, Chinese Herbal; D007371:Interferon-gamma; D007378:Interleukins; D012333:RNA, Messenger; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014315:Triterpenes; D000097245:Ursolic Acid; C495342:TLR2 protein, human; C495345:TLR4 protein, human