title: Anti-invasive effects of Celastrus Orbiculatus extract on interleukin-1 beta and tumour necrosis factor-alpha combination-stimulated fibroblast-like synoviocytes.
abstract: BACKGROUND
  Invasion of fibroblast-like synoviocytes (FLSs) is critical in the pathogenesis of rheumatoid arthritis (RA). The metalloproteinases (MMPs) and activator of nuclear factor-kappa B (NF-κB) pathway play a critical role in RA-FLS invasion induced by interleukin-1 beta (IL-1β) and tumour necrosis factor-alpha (TNF-α). The present study aimed to explore the anti-invasive activity and mechanism of Celastrus orbiculatus extract (COE) on IL-1β and TNF-α combination-stimulated human RA-FLSs.
  
  
  METHODS
  We investigated the effect of COE on IL-1β and TNF-α combination-induced FLS invasion as well as MMP expression and explored upstream signal transduction.
  
  
  RESULTS
  COE suppressed IL-1β and TNF-α combination-stimulated FLSs invasion by inhibiting MMP-9 expression and activity. Furthermore, our results revealed that COE inhibited the transcriptional activity of MMP-9 by suppression of the binding activity of NF-κB in the MMP-9 promoter, and inhibited IκBα phosphorylation and nuclear translocation of NF-κB.
  
  
  CONCLUSIONS
  COE inhibits IL-1β and TNF-α combination-induced FLSs invasion by suppressing NF-κB-mediated MMP-9 expression.
authors.affiliation: Department of Rheumatology, Clinical Medical College, Yangzhou University, Yangzhou 225000, China. guoqing1007@163.com.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Li
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.forename: Shiyu
authors.initials: S
authors.lastname: Guo
authors.forename: Masataka
authors.initials: M
authors.lastname: Sunagawa
authors.forename: Tadashi
authors.initials: T
authors.lastname: Hisamitsu
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Liu
mesh_terms: D018501:Antirheumatic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000517:prevention & control; D031247:Celastrus; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism* / Q000494:pharmacology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D015398:Signal Transduction; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D018501:Antirheumatic Agents; D020672:I-kappa B Proteins; D053583:Interleukin-1beta; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D010936:Plant Extracts; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D020780:Matrix Metalloproteinase 9