title: Ascophyllan purified from Ascophyllum nodosum induces Th1 and Tc1 immune responses by promoting dendritic cell maturation.
abstract: Marine-derived sulfated polysaccharides have been shown to possess certain anti-virus, anti-tumor, anti-inflammatory and anti-coagulant activities. However, the in vivo immunomodulatory effects of marine-derived pure compounds have been less well characterized. In this study, we investigated the effect of ascophyllan, a sulfated polysaccharide purified from Ascophyllum nodosum, on the maturation of mouse dendritic cells (DCs) in vitro and in vivo. Ascophyllan induced up-regulation of co-stimulatory molecules and production of pro-inflammatory cytokines in bone marrow-derived DCs (BMDCs). Moreover, in vivo administration of ascophyllan promotes up-regulation of CD40, CD80, CD86, MHC class I and MHC class II and production of IL-6, IL-12 and TNF-α in spleen cDCs. Interestingly, ascophyllan induced a higher degree of co-stimulatory molecule up-regulation and pro-inflammatory cytokine production than fucoidan, a marine-derived polysaccharide with well-defined effect for promoting DC maturation. Ascophyllan also promoted the generation of IFN-γ-producing Th1 and Tc1 cells in the presence of DCs in an IL-12-dependent manner. Finally, myeloid differentiation primary response 88 (MyD88) signaling pathway was essential for DC maturation induced by ascophyllan. Taken together, these results demonstrate that ascophyllan induces DC maturation, and consequently enhances Th1 and Tc1 responses in vivo. This knowledge could facilitate the development of novel therapeutic strategies to combat infectious diseases and cancer.
authors.affiliation: Shanghai Public Health Clinical Center, Shanghai Medical College, Fudan University, Shanghai 201508, China. weiwei061215@126.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Shanghai Public Health Clinical Center, Shanghai Medical College, Fudan University, Shanghai 201508, China. dujiangyuan@shaphc.org.
authors.forename: Jiang-Yuan
authors.initials: JY
authors.lastname: Du
authors.affiliation: Division of Biochemistry, Faculty of Fisheries, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan. zdjiang1982@hotmail.com.
authors.forename: Zedong
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Research and Development Division, Hayashikane Sangyo Co., Ltd., Shimonoseki, Yamaguchi 750-8608, Japan. tokimura@hayashikane.co.jp.
authors.forename: Takasi
authors.initials: T
authors.lastname: Okimura
authors.affiliation: Division of Biochemistry, Faculty of Fisheries, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan. t-oda@nagasaki-u.ac.jp.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Oda
authors.affiliation: Department of Immunology and Infectious Diseases, The Forsyth Institute, 245 First Street, Cambridge, MA 02142, USA. qyu@forsyth.org.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yu
authors.affiliation: Shanghai Public Health Clinical Center, Shanghai Medical College, Fudan University, Shanghai 201508, China. junojin1@gmail.com.
authors.forename: Jun-O
authors.initials: JO
authors.lastname: Jin
mesh_terms: D000818:Animals; D044646:Ascophyllum / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000187:drug effects* / Q000502:physiology; D018664:Interleukin-12 / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000502:physiology; D011134:Polysaccharides / Q000302:isolation & purification / Q000494:pharmacology*; D015398:Signal Transduction; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology
chemical_list: D016207:Cytokines; D053594:Myeloid Differentiation Factor 88; D011134:Polysaccharides; C058519:ascophyllin; D018664:Interleukin-12