title: Inhibitory effects of niclosamide on inflammation and migration of fibroblast-like synoviocytes from patients with rheumatoid arthritis.
abstract: OBJECTIVE
  This study evaluated the anti-inflammatory effect of niclosamide in tumor necrosis factor (TNF)-α-stimulated human rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) and inhibitory effects on migration and invasion in RA FLS and investigated the signal mechanism, and further explored the treatment activity of niclosamide on collagen-induced arthritis (CIA).
  
  
  METHODS
  The levels of interleukin (IL)-1β, IL-6, IL-8, IL-10,IL-17A and interferon (IFN)-γ in cultural supernatants were measured by multiplex cytokine assay kits. RA FLS migration and invasion in vitro were measured by the Boyden chamber method and the scratch assay. Signal transduction proteins expression was measured by western blot. The in vivo suppressive effects of niclosamide were elucidated on CIA in a mouse model.
  
  
  RESULTS
  Niclosamide reduced the secretion of IL-1β, IL-6, IL-8, IL-17A and IFN-γ from TNF-α-induced RA FLS in a dose-dependent manner. Niclosamide inhibits FBS-induced migration and invasion and exhibits F-actin alterations in RA FLS. Niclosamide decreased the phosphorylation of c-Jun N-terminal kinase and ERK in TNF-α-stimulated RA FLS and blocked TNF-α-induced IKK, IκBα phosphorylation and translocation of p65. Niclosamide treatments reduced the severity of CIA model.
  
  
  CONCLUSIONS
  Our data suggest for the first time that niclosamide posses the anti-inflammatory effect in RA both in vitro and in vivo.
authors.affiliation: Department of Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, No. 58 Zhongshan Road 2, Guangzhou, 510080, Guangdong, People's Republic of China.
authors.forename: Liuqin
authors.initials: L
authors.lastname: Liang
authors.forename: Mingcheng
authors.initials: M
authors.lastname: Huang
authors.forename: Youjun
authors.initials: Y
authors.lastname: Xiao
authors.forename: Shan
authors.initials: S
authors.lastname: Zen
authors.forename: Minxu
authors.initials: M
authors.lastname: Lao
authors.forename: Yaoyao
authors.initials: Y
authors.lastname: Zou
authors.forename: Maohua
authors.initials: M
authors.lastname: Shi
authors.forename: Xiuyan
authors.initials: X
authors.lastname: Yang
authors.forename: Hanshi
authors.initials: H
authors.lastname: Xu
mesh_terms: D000818:Animals; D000923:Anticestodal Agents / Q000494:pharmacology / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D009534:Niclosamide / Q000494:pharmacology* / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D013583:Synovial Membrane / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D000923:Anticestodal Agents; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D009534:Niclosamide; D020929:Mitogen-Activated Protein Kinase Kinases