title: Polyacetylenediols regulate the function of human monocyte-derived dendritic cells.
abstract: Callyspongidiol and 14,15-dihydrosiphonodiol are Polyacetylenediols isolated from marine sponges and are pharmacologically active substances. Dendritic cells (DC) play an important role in the initiation and regulation of immune response. DC have a key influence in the differentiation of naïve T cells into Th1, Th2 or Th17 effector cells. We demonstrated that callyspongidiol and 14,15-dihydrosiphonodiol activate human DC as documented by phenotypic and functional maturation, and altered cytokine production. Up regulation of cell surface expression of CD1a, CD80, CD83, CD86, HLA-DR and CCR7 was observed following DC treatment with callyspongidiol and 14,15-dihydrosiphonodiol. The production of IL-10 by callyspongidiol-primed DC after stimulation with CD40-L was higher than that of LPS- or 14,15-dihydrosiphonodiol-primed DC. Naïve T cells co-cultured with allogeneic 14,15-dihydrosiphonodiol-primed DC at 1:5 DC/T cell ratio turned into typical Th1 cells depending on IL-12 secretion and independent on TLR2 or TLR4. In contrast, callyspongidiol-primed DC co-cultured with naïve T cells secreted IL-4 and IL-10, but had little effect on IFN-gamma. Callyspongidiol-primed DC induced the development of Th2 cells via the inhibition of IL-12p70 and the enhancement of IL-10. Polyacetylenediols-primed DC expressed the chemokine receptor CCR7 and had a high migration to CCL19. These results suggested that some Polyacetylenediols modulate human DC function in a fashion that favors Th1/Th2 cell polarization or IL-10 producing T cells, and might have implication in tumor or in autoimmune diseases.
authors.affiliation: Division of Cellular Allergology, Research Center Borstel, Parkallee 22, D-23845 Borstel, Germany. mtakei@pep.ne.jp
authors.forename: Masao
authors.initials: M
authors.lastname: Takei
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
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D056747:Immunomodulation; D008213:Lymphocyte Activation / Q000187:drug effects; D009000:Monocytes / Q000473:pathology; D053279:Polyynes / Q000494:pharmacology*; D011161:Porifera / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D058408:Th1-Th2 Balance / Q000187:drug effects
chemical_list: C548230:14,15-dihydrosiphonodiol; D000943:Antigens, Differentiation; D016207:Cytokines; C548229:callyspongidiol; D053279:Polyynes