title: Antihelminthic niclosamide modulates dendritic cells activation and function.
abstract: 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-γ 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-κB 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.
authors.affiliation: 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.
authors.forename: Chieh-Shan
authors.initials: CS
authors.lastname: Wu
authors.affiliation: Institute of Biomedical Science, National Chung-Hsing University, Taichung, Taiwan, ROC.
authors.forename: Yi-Rong
authors.initials: YR
authors.lastname: Li
authors.affiliation: Institute of Biomedical Science, National Chung-Hsing University, Taichung, Taiwan, ROC; Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taiwan, ROC.
authors.forename: Jeremy J W
authors.initials: JJ
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Science, National Chung-Hsing University, Taichung, Taiwan, ROC.
authors.forename: Ying-Che
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei 100, Taiwan, ROC.
authors.forename: Chiang-Liang
authors.initials: CL
authors.lastname: Chu
authors.affiliation: Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu, Taiwan, ROC.
authors.forename: I-Hong
authors.initials: IH
authors.lastname: Pan
authors.affiliation: Department of Chemistry, Tunghai University, Taichung, Taiwan, ROC.
authors.forename: Yu-Shan
authors.initials: YS
authors.lastname: Wu
authors.affiliation: 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.
authors.forename: Chi-Chen
authors.initials: CC
authors.lastname: Lin
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000276:immunology / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D004139:Dinitrofluorobenzene / Q000008:administration & dosage / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation; D006967:Hypersensitivity / Q000276:immunology / Q000517:prevention & control*; D007114:Immunization; D056747:Immunomodulation / Q000187:drug effects; D007275:Injections, Intravenous; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000276:immunology; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D009534:Niclosamide / Q000276:immunology / Q000494:pharmacology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology
chemical_list: D000871:Anthelmintics; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009534:Niclosamide; D004139:Dinitrofluorobenzene; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases
keywords: Contact hypersensitivity (CHS); Cytokine; Dendritic cells; Niclosamide; T cell proliferation