PMID- 24859056 OWN - NLM STAT- MEDLINE DCOM- 20150409 LR - 20140722 IS - 1878-1705 (Electronic) IS - 1567-5769 (Linking) VI - 21 IP - 2 DP - 2014 Aug TI - Enhanced dendritic cell maturation by the B-chain of Korean mistletoe lectin (KML-B), a novel TLR4 agonist. PG - 309-19 LID - S1567-5769(14)00182-9 [pii] LID - 10.1016/j.intimp.2014.05.010 [doi] AB - 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-1beta, IL-6, IL-12p70, and TNF-alpha) 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 naive 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. CI - Copyright (c) 2014 Elsevier B.V. All rights reserved. FAU - Kim, Jong-Jin AU - Kim JJ AD - Department of Biology, Sunchon National University, Suncheon, Republic of Korea. FAU - Hwang, Yun-Ho AU - Hwang YH AD - Department of Pharmacy, Sunchon National University, Suncheon, Republic of Korea. FAU - Kang, Kyung-Yun AU - Kang KY AD - Department of Pharmacy, Sunchon National University, Suncheon, Republic of Korea. FAU - Kim, Inbo AU - Kim I AD - School of Life Science, Handong Global University, Pohang, Republic of Korea. FAU - Kim, Jong-Bae AU - Kim JB AD - School of Life Science, Handong Global University, Pohang, Republic of Korea. FAU - Park, Jong-Hwan AU - Park JH AD - Department of Biochemistry, College of Medicine, Konyang University, Daejeon, Republic of Korea. FAU - Yoo, Yung-Choon AU - Yoo YC AD - Department of Microbiology, College of Medicine, Konyang University, Daejeon, Republic of Korea. FAU - Yee, Sung-Tae AU - Yee ST AD - 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. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140521 PL - Netherlands TA - Int Immunopharmacol JT - International immunopharmacology JID - 100965259 RN - 0 (Adjuvants, Immunologic) RN - 0 (Antigens, CD) RN - 0 (Interleukins) RN - 0 (Lectins) RN - 0 (Tlr4 protein, mouse) RN - 0 (Toll-Like Receptor 4) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Adjuvants, Immunologic/pharmacology MH - Animals MH - Antigens, CD/metabolism MH - Bone Marrow Cells/drug effects/metabolism MH - Cell Differentiation/drug effects MH - Dendritic Cells/*drug effects/metabolism MH - Female MH - Humans MH - Interleukins/metabolism MH - Lectins/*pharmacology MH - Lymphocyte Activation/*drug effects MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Mistletoe/*chemistry MH - Th1 Cells/drug effects/metabolism MH - Toll-Like Receptor 4/*analysis MH - Tumor Necrosis Factor-alpha/metabolism OTO - NOTNLM OT - BMDCs (bone marrow-derived dendritic cells) OT - CD4(+) T cells OT - KML (Korean mistletoe lectin) OT - KML-B (B-chain of KML) OT - TLR4 (toll-liked receptor 4) EDAT- 2014/05/27 06:00 MHDA- 2015/04/10 06:00 CRDT- 2014/05/27 06:00 PHST- 2014/03/20 00:00 [received] PHST- 2014/04/24 00:00 [revised] PHST- 2014/05/06 00:00 [accepted] PHST- 2014/05/27 06:00 [entrez] PHST- 2014/05/27 06:00 [pubmed] PHST- 2015/04/10 06:00 [medline] AID - S1567-5769(14)00182-9 [pii] AID - 10.1016/j.intimp.2014.05.010 [doi] PST - ppublish SO - Int Immunopharmacol. 2014 Aug;21(2):309-19. doi: 10.1016/j.intimp.2014.05.010. Epub 2014 May 21.