title: Curdlan activates dendritic cells through dectin-1 and toll-like receptor 4 signaling.
abstract: Curdlan, a β-1,3-glucan isolated from Alcaligenes faecalis, is an agonist of dectin-1 in various immune cells, including dendritic cells (DCs). However, whether curdlan also activates DCs through other receptors remains unknown. In this study, we found that curdlan activates DCs through dectin-1 and toll-like receptor 4 (TLR4). Curdlan increased the expression levels of surface molecules (CD40, CD80, CD86, and MHC-I/II), the production of cytokines (IL-12, IL-1β, TNF-α, and IFN-β), migration toward MIP-3β, and allogeneic T cell stimulation activity of DCs. Curdlan increased the phosphorylation of Syk, Raf-1, Akt, MAPKs, IKK, and NF-κB p65 in DCs. However, curdlan only slightly activated DCs transfected with small interfering RNAs against dectin-1 or TLR4 and C3H/HeJ DCs, which have non-functional TLR4, in comparison with control DCs. Curdlan increased antitumor activity of DCs in a syngeneic tumor model. In summary, our data show that curdlan activates DCs through dectin-1 and TLR4 signaling and the combination of curdlan and DCs efficiently inhibit tumor growth in mice.
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 28644, Republic of Korea.
authors.forename: Hyung Sook
authors.initials: HS
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 28644, Republic of Korea.
authors.forename: Ki Hwan
authors.initials: KH
authors.lastname: Park
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 28644, Republic of Korea.
authors.forename: Hong Kyung
authors.initials: HK
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 28644, Republic of Korea.
authors.forename: Ji Sung
authors.initials: JS
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 28644, Republic of Korea.
authors.forename: Yong Guk
authors.initials: YG
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 28644, Republic of Korea.
authors.forename: Jae Hee
authors.initials: JH
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 28644, Republic of Korea.
authors.forename: Ki Hun
authors.initials: KH
authors.lastname: Kim
authors.affiliation: Korea Research Institute of Bioscience and Biotechnology, Cheongju, Chungbuk 28116, Republic of Korea.
authors.forename: Jieun
authors.initials: J
authors.lastname: Yun
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 28644, Republic of Korea.
authors.forename: Bang Yeon
authors.initials: BY
authors.lastname: Hwang
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 28644, Republic of Korea.
authors.forename: Jin Tae
authors.initials: JT
authors.lastname: Hong
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 28644, Republic of Korea.
authors.forename: Youngsoo
authors.initials: Y
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju, Chungbuk 28644, Republic of Korea. Electronic address: shan@chungbuk.ac.kr.
authors.forename: Sang-Bae
authors.initials: SB
authors.lastname: Han
mesh_terms: D042481:Alcaligenes faecalis / Q000276:immunology*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D002465:Cell Movement / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000502:physiology; D018836:Inflammation Mediators / Q000378:metabolism; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D008213:Lymphocyte Activation; D008546:Melanoma, Experimental; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D034741:RNA, Small Interfering / Q000235:genetics; D012878:Skin Neoplasms / Q000188:drug therapy*; D013601:T-Lymphocytes / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D047071:beta-Glucans / Q000627:therapeutic use*; D000099181:Dectin-1
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; D018836:Inflammation Mediators; D037181:Lectins, C-Type; D034741:RNA, Small Interfering; D051197:Toll-Like Receptor 4; D047071:beta-Glucans; D000099181:Dectin-1; C493487:Tlr4 protein, mouse; C038459:curdlan
keywords: Adjuvant; C3H/HeJ; Cancer immunotherapy; siRNA