title: CCL-34, a synthetic toll-like receptor 4 activator, modulates differentiation and maturation of myeloid dendritic cells.
abstract: CCL-34, a synthetic α-galactosylceramide analog, has been reported as an activator of toll-like receptor 4 (TLR4) in macrophages. TLR4 is highly expressed in dendritic cell (DC) and several TLR4 agonists are known to trigger DC maturation. We herein evaluated the effect of CCL-34 on DC maturation. Human CD14+ monocyte-derived immature DC were treated with CCL-34, its inactive structural analog CCL-44, or LPS to assess the DC maturation. CCL-34 induced DC maturation according to their characteristically dendrite-forming morphology, CD83 expression and IL-12p70 production. The allostimulatory activity of DC on proliferation of naive CD4+CD45+RA+ T cells and their secretion of interferon-γ was increased by CCL-34. Phagocytosis, an important function of immature DC, was reduced after CCL-34 treatment. All these effects related to DC maturation were evidently induced by positive control LPS but not by CCL-44 treatment. TLR4 neutralization impaired human DC maturation triggered by CCL-34. The induction of IL-12, a hallmark of DC maturation, by CCL-34 and LPS was only evident in TLR4-competent C3H/HeN, but not in TLR4-defective C3H/HeJ mice. CCL-34 could further elicit the antigen presentation capability in mice inoculated with doxorubicin-treated colorectal cancer cells. In summary, CCL-34 triggers DC maturation via a TLR4-dependent manner, which supports its potential application as an immunostimulator.
authors.affiliation: Institute of Traditional Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Shu-Ling
authors.initials: SL
authors.lastname: Fu
authors.affiliation: Department of Chemistry, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Chun-Cheng
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan.
authors.forename: Ming-Ling
authors.initials: ML
authors.lastname: Hsu
authors.affiliation: Institute of Traditional Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Sheng-Hung
authors.initials: SH
authors.lastname: Liu
authors.affiliation: School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan.
authors.forename: Yu-Chuen
authors.initials: YC
authors.lastname: Huang
authors.affiliation: Institute of Traditional Medicine, National Yang-Ming University, Taipei, Taiwan.|Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan.|Department of Radiation Oncology, MacKay Memorial Hospital, Taipei, Taiwan.
authors.forename: Yu-Jen
authors.initials: YJ
authors.lastname: Chen
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects*; D006017:Glycolipids / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D022423:Myeloid Cells / Q000166:cytology / Q000187:drug effects*; D012694:Serine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C570114:CCL 34; D006017:Glycolipids; D012694:Serine
keywords: CCL-34; TLR4; dendritic cell; differentiation; maturation