title: Enhanced dendritic cell maturation by the B-chain of Korean mistletoe lectin (KML-B), a novel TLR4 agonist.
abstract: Korean mistletoe lectin (KML) is composed of A and B sub-chains. The B-chain binds to cell surfaces, whereas the A-chain hinders translation because it is a RIP (ribosome inactivating protein) inducing apoptosis. Although KML has various biological and immunological activities, its potential use in cancer therapy or as an adjuvant therapy is limited by its toxicity to normal cells. This study was conducted to determine whether the B-chain of KML (KML-B) has immunoadjuvant activity and cytotoxicity activity. To evaluate the immunomodulatory activities of B chain KML, in vitro experiments employing bone marrow-derived dendritic cells (BMDCs) were performed. Dendritic cells (DCs) are a unique group of white blood cells that are able to capture and process antigens for presentation to T cells, which constitute primary immune response. In the present study, KML-B was found to be non-cytotoxic to BMDCs. Furthermore, the expressions of co-stimulatory molecules (CD40, CD80, CD86, and MHC II) and the secretions of cytokines (IL-1β, IL-6, IL-12p70, and TNF-α) were increased in BMDCs by KML-B. In addition, other indicators (antigen-uptake and CCR7 expression) of BMDC maturation were changed by KML-B, and the ability of KML-B to enhance various functions by BMDCs was found to be dependent on TLR4 expression. Moreover, BMDCs matured by KML-B induced naïve CD4(+) T cell differentiation toward Th1 cells directly and indirectly. These experiments confirm that KML-B exhibits potent immunomodulatory properties and suggest that KML-B be considered a potential dendritic cell-based cancer therapy and immunoadjuvant.
authors.affiliation: Department of Biology, Sunchon National University, Suncheon, Republic of Korea.
authors.forename: Jong-Jin
authors.initials: JJ
authors.lastname: Kim
authors.affiliation: Department of Pharmacy, Sunchon National University, Suncheon, Republic of Korea.
authors.forename: Yun-Ho
authors.initials: YH
authors.lastname: Hwang
authors.affiliation: Department of Pharmacy, Sunchon National University, Suncheon, Republic of Korea.
authors.forename: Kyung-Yun
authors.initials: KY
authors.lastname: Kang
authors.affiliation: School of Life Science, Handong Global University, Pohang, Republic of Korea.
authors.forename: Inbo
authors.initials: I
authors.lastname: Kim
authors.affiliation: School of Life Science, Handong Global University, Pohang, Republic of Korea.
authors.forename: Jong-Bae
authors.initials: JB
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, College of Medicine, Konyang University, Daejeon, Republic of Korea.
authors.forename: Jong-Hwan
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Microbiology, College of Medicine, Konyang University, Daejeon, Republic of Korea.
authors.forename: Yung-Choon
authors.initials: YC
authors.lastname: Yoo
authors.affiliation: Department of Biology, Sunchon National University, Suncheon, Republic of Korea; Department of Pharmacy, Sunchon National University, Suncheon, Republic of Korea. Electronic address: sungtae@sunchon.ac.kr.
authors.forename: Sung-Tae
authors.initials: ST
authors.lastname: Yee
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D007378:Interleukins / Q000378:metabolism; D037102:Lectins / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D014784:Mistletoe / Q000737:chemistry*; D018417:Th1 Cells / Q000187:drug effects / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000032:analysis*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D007378:Interleukins; D037102:Lectins; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha
keywords: BMDCs (bone marrow-derived dendritic cells); CD4(+) T cells; KML (Korean mistletoe lectin); KML-B (B-chain of KML); TLR4 (toll-liked receptor 4)