PMID- 24561310 OWN - NLM STAT- MEDLINE DCOM- 20140529 LR - 20211021 IS - 1090-2163 (Electronic) IS - 0008-8749 (Print) IS - 0008-8749 (Linking) VI - 288 IP - 1-2 DP - 2014 Mar-Apr TI - Antihelminthic niclosamide modulates dendritic cells activation and function. PG - 15-23 LID - S0008-8749(13)00206-2 [pii] LID - 10.1016/j.cellimm.2013.12.006 [doi] AB - Dendritic cells (DCs) link the sensing of the environment by the innate immune system to the initiation of adaptive immune responses. Accordingly, DCs are considered to be a major target in the development of immunomodulating compounds. In this study, the effect of niclosamide, a Food and Drug Administration-approved antihelminthic drug, on the activation of lipopolysaccharide (LPS)-stimulated murine bone marrow-derived DCs was examined. Our experimental results show that niclosamide reduced the pro-inflammatory cytokine and chemokine expression of LPS-activated DCs. In addition, niclosamide also affected the expression of MHC and costimulatory molecules and influenced the ability of the cells to take up antigens. Therefore, in mixed cell cultures composed of syngeneic OVA-specific T cells and DCs, niclosamide-treated DCs showed a decreased ability to stimulate T cell proliferation and IFN-gamma production. Furthermore, intravenous injection of niclosamide also attenuated contact hypersensitivity (CHS) in mice during sensitization with 2,4-dinitro-1-fluorobenzene. Blocking the LPS-induced activation of MAPK-ERK, JNK and NF-kappaB may contribute to the inhibitory effect of niclosamide on DC activation. Collectively, our findings suggest that niclosamide can manipulate the function of DCs. These results provide new insight into the immunopharmacological role of niclosamide and suggest that it may be useful for the treatment of chronic inflammatory disorders or DC-mediated autoimmune diseases. CI - Copyright (c) 2014 Elsevier Inc. All rights reserved. FAU - Wu, Chieh-Shan AU - Wu CS AD - Department of Dermatology, Kaohsiung Veterans General Hospital, Taiwan, ROC; Department of Dermatology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Taiwan, ROC; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Taiwan, ROC. FAU - Li, Yi-Rong AU - Li YR AD - Institute of Biomedical Science, National Chung-Hsing University, Taichung, Taiwan, ROC. FAU - Chen, Jeremy J W AU - Chen JJ AD - Institute of Biomedical Science, National Chung-Hsing University, Taichung, Taiwan, ROC; Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taiwan, ROC. FAU - Chen, Ying-Che AU - Chen YC AD - Institute of Biomedical Science, National Chung-Hsing University, Taichung, Taiwan, ROC. FAU - Chu, Chiang-Liang AU - Chu CL AD - Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei 100, Taiwan, ROC. FAU - Pan, I-Hong AU - Pan IH AD - Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu, Taiwan, ROC. FAU - Wu, Yu-Shan AU - Wu YS AD - Department of Chemistry, Tunghai University, Taichung, Taiwan, ROC. FAU - Lin, Chi-Chen AU - Lin CC AD - Institute of Biomedical Science, National Chung-Hsing University, Taichung, Taiwan, ROC; Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taiwan, ROC; Department of Medical Research and Education, Taichung Veterans General Hospital, Taichung, Taiwan, ROC; Division of Chest Medicine, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan, ROC. Electronic address: lincc@dragon.nchu.edu.tw. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131228 PL - Netherlands TA - Cell Immunol JT - Cellular immunology JID - 1246405 RN - 0 (Anthelmintics) RN - 0 (Lipopolysaccharides) RN - 0 (NF-kappa B) RN - 8KK8CQ2K8G (Niclosamide) RN - D241E059U6 (Dinitrofluorobenzene) RN - EC 2.7.12.2 (MAP Kinase Kinase 4) RN - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases) SB - IM MH - Animals MH - Anthelmintics/immunology/*pharmacology MH - Bone Marrow Cells/cytology/*drug effects/immunology MH - Cell Proliferation/drug effects MH - Cells, Cultured MH - Coculture Techniques MH - Dendritic Cells/cytology/*drug effects/immunology MH - Dinitrofluorobenzene/administration & dosage/immunology MH - Female MH - Gene Expression Regulation MH - Hypersensitivity/immunology/*prevention & control MH - Immunization MH - Immunomodulation/drug effects MH - Injections, Intravenous MH - Lipopolysaccharides/pharmacology MH - Lymphocyte Activation/drug effects MH - MAP Kinase Kinase 4/genetics/immunology MH - Mice MH - Mice, Inbred C57BL MH - Mitogen-Activated Protein Kinase Kinases/genetics/immunology MH - NF-kappa B/genetics/immunology MH - Niclosamide/immunology/*pharmacology MH - Signal Transduction MH - T-Lymphocytes/cytology/*drug effects/immunology PMC - PMC7094312 OTO - NOTNLM OT - Contact hypersensitivity (CHS) OT - Cytokine OT - Dendritic cells OT - Niclosamide OT - T cell proliferation EDAT- 2014/02/25 06:00 MHDA- 2014/05/30 06:00 PMCR- 2013/12/28 CRDT- 2014/02/25 06:00 PHST- 2013/09/23 00:00 [received] PHST- 2013/12/04 00:00 [revised] PHST- 2013/12/11 00:00 [accepted] PHST- 2014/02/25 06:00 [entrez] PHST- 2014/02/25 06:00 [pubmed] PHST- 2014/05/30 06:00 [medline] PHST- 2013/12/28 00:00 [pmc-release] AID - S0008-8749(13)00206-2 [pii] AID - 10.1016/j.cellimm.2013.12.006 [doi] PST - ppublish SO - Cell Immunol. 2014 Mar-Apr;288(1-2):15-23. doi: 10.1016/j.cellimm.2013.12.006. Epub 2013 Dec 28.