title: Simvastatin induces apoptosis of fibroblast-like synoviocytes.
abstract: BACKGROUND
  Statins (3-Hydroxy-3-methylglutaryl-CoA reductase inhibitors) exert favorable effects on lipoprotein metabolism, but appeared to possess anti-inflammatory properties among others, as suggested by their ability to inhibit collagen-induced arthritis in mice. Their activity in fibroblast-like synovial cells (FLS) has not yet been studied.
  
  
  OBJECTIVE
  To evaluate the effect of varying doses of simvastatin on apoptosis of FLS.
  
  
  METHODS
  Synovial tissue, obtained during total knee replacement due to osteoarthritis, was cut into small pieces and cultured in Petri dishes with test materials, as previously described. FLS were incubated for 48 hours with 1 mumol/ml, 5 mumol/ ml, 15 mumol/ml and 50 mumol/ml of simvastatin. Following incubation, apoptosis was analyzed by two-dimensional flow cytometry (FACS) using annexin V/PI staining according to the manufacturer's instructions.
  
  
  RESULTS
  Different concentrations of simvastatin induced apoptosis of FLS. The level proportion of apoptotic cells of resting or activated with lipopolysaccharide (LPS; 3 mug/ml) FLS, not treated with simvastatin, was 21%. At 48 hours, the rate of apoptosis of activated fibroblasts, incubated with 1 mumol/ml, 5 mumol/ml, 15 and 50 mumol/ml was 22%, 32%, 48% and 41% respectively. Synovial cell viability evaluated by tetrazolium salt XXT was unaffected by the simvastatin concentration used.
  
  
  CONCLUSIONS
  Varying concentrations of simvastatin induce apoptosis of activated fibroblast-like synoviocytes, suggesting another possible mechanism of anti-inflammatory effects of statins in inflammatory conditions.
authors.affiliation: Department of Rheumatology, Sourasky Medical Center and Sackler Faculty of Medicine, University of Tel Aviv, Tel Aviv, Israel.
authors.forename: Ira
authors.initials: I
authors.lastname: Litinsky
authors.forename: Itshak
authors.initials: I
authors.lastname: Golan
authors.forename: Michael
authors.initials: M
authors.lastname: Yaron
authors.forename: Ilana
authors.initials: I
authors.lastname: Yaron
authors.forename: Dan
authors.initials: D
authors.lastname: Caspi
authors.forename: Ori
authors.initials: O
authors.lastname: Elkayam