title: Validity of SW982 synovial cell line for studying the drugs against rheumatoid arthritis in fluvastatin-induced apoptosis signaling model.
abstract: OBJECTIVE
  To study effects of drugs against rheumatoid arthritis (RA) synoviocytes or fibroblast like synoviocytes (FLS) are used. To overcome the drawbacks of using FLS, this study was conducted to show the validity of SW982 synovial cell line in RA study.
  
  
  METHODS
  3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, Annexin V propidium iodide (PI) staining, mitochondrial membrane potential assay, Triton X-114 Phase partitioning, and immunolot for apoptosis signaling in SW982 human synovial cell line were performed.
  
  
  RESULTS
  Fluvastatin induced apoptosis in a dose- and time-dependent manner in TNFα -stimulated SW982 human synovial cells. A geranylgeranylpyrophosphate (GGPP) inhibitor, but not a farnesylpyrophosphate (FPP) inhibitor, induced apoptosis, and fluvastatin-induced apoptosis was associated with the translocation of isoprenylated RhoA and Rac1 proteins from the cell membrane to the cytosol. Fluvastatin-induced downstream apoptotic signals were associated with inhibition of the phosphoinositide 3-kinase (PI3K)/Akt pathway. Accordingly, 89 kDa apoptotic cleavage fragment of poly (ADP-ribose) polymerase (PARP) was detected.
  
  
  CONCLUSIONS
  Collectively, our data indicate that fluvastatin induces apoptotic cell death in TNFα-stimulated SW982 human synovial cells through the inactivation of the geranylgerenylated membrane fraction of RhoA and Rac1 proteins and the subsequent inhibition of the PI3K/Akt signaling pathway. This finding shows the validity of SW982 cell line for RA study.
authors.forename: Jae-Ho
authors.initials: JH
authors.lastname: Chang
authors.forename: Kyu-Jae
authors.initials: KJ
authors.lastname: Lee
authors.affiliation: Institute of Biomaterials, Yonsei University; Department of Microbiology, Yonsei University Wonju College of Medicine, Wonju, Korea.
authors.forename: Soo-Ki
authors.initials: SK
authors.lastname: Kim
authors.forename: Dae-Hyun
authors.initials: DH
authors.lastname: Yoo
authors.affiliation: Department of Rheumatology, Yonsei University Wonju College of Medicine, Wonju, Korea.
authors.forename: Tae-Young
authors.initials: TY
authors.lastname: Kang
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000473:pathology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005229:Fatty Acids, Monounsaturated / Q000008:administration & dosage*; D000077340:Fluvastatin; D006801:Humans; D007211:Indoles / Q000008:administration & dosage*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D011106:Polyisoprenyl Phosphates / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects; D013582:Synovial Fluid / Q000166:cytology / Q000187:drug effects; D013778:Tetrazolium Salts / Q000008:administration & dosage; D013844:Thiazoles / Q000008:administration & dosage
chemical_list: D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D011106:Polyisoprenyl Phosphates; D013778:Tetrazolium Salts; D013844:Thiazoles; D000077340:Fluvastatin; C022616:thiazolyl blue; C002963:geranylgeranyl pyrophosphate