Display options
Share it on

Open Rheumatol J. 2009 Sep 07;3:35-40. doi: 10.2174/1874312900903010035.

Simvastatin induces apoptosis of fibroblast-like synoviocytes.

The open rheumatology journal

Ira Litinsky, Itshak Golan, Michael Yaron, Ilana Yaron, Dan Caspi, Ori Elkayam

Affiliations

  1. Department of Rheumatology, Sourasky Medical Center and Sackler Faculty of Medicine, University of Tel Aviv, Tel Aviv, Israel.

PMID: 19771181 PMCID: PMC2746119 DOI: 10.2174/1874312900903010035

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.

OBJECTIVES: 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.

CONCLUSION: Varying concentrations of simvastatin induce apoptosis of activated fibroblast-like synoviocytes, suggesting another possible mechanism of anti-inflammatory effects of statins in inflammatory conditions.

Keywords: Apoptosis; fibroblast-like synoviocytes.; inflammation; simvastatin

References

  1. Lupus. 2005;14(3):192-6 - PubMed
  2. Nature. 2002 Nov 7;420(6911):78-84 - PubMed
  3. Am Heart J. 2004 Aug;148(2):200-10 - PubMed
  4. Atherosclerosis. 2003 Aug;169(2):251-8 - PubMed
  5. Lab Invest. 1962 Sep;11:703-13 - PubMed
  6. Arthritis Rheum. 2001 Dec;44(12):2737-45 - PubMed
  7. Circulation. 2001 Mar 6;103(9):1191-3 - PubMed
  8. Am J Respir Crit Care Med. 1998 May;157(5 Pt 1):1616-22 - PubMed
  9. Leukemia. 2002 Jul;16(7):1362-71 - PubMed
  10. Biochem Biophys Res Commun. 1994 Dec 30;205(3):1681-7 - PubMed
  11. Cancer Res. 2005 Mar 1;65(5):1952-60 - PubMed
  12. Ann Rheum Dis. 1993 Mar;52 Suppl 1:S39-47 - PubMed
  13. JAMA. 1998 May 27;279(20):1615-22 - PubMed
  14. Lancet. 1999 Mar 20;353(9157):983-4 - PubMed
  15. J Immunol. 2003 Feb 1;170(3):1524-30 - PubMed
  16. Fundam Clin Pharmacol. 2005 Feb;19(1):81-5 - PubMed
  17. J Rheumatol. 2008 Feb;35(2):193-200 - PubMed
  18. J Immunol Methods. 1991 Sep 13;142(2):257-65 - PubMed
  19. Z Kardiol. 2004 May;93(5):398-402 - PubMed
  20. Atherosclerosis. 1998 Dec;141(2):203-7 - PubMed
  21. Arthritis Rheum. 2005 Jan;52(1):61-72 - PubMed
  22. Endocrinology. 1999 Feb;140(2):698-704 - PubMed
  23. Arthritis Rheum. 2006 Feb;54(2):579-86 - PubMed
  24. Immunol Today. 1995 Jan;16(1):39-43 - PubMed
  25. Curr Atheroscler Rep. 2002 Jan;4(1):42-7 - PubMed
  26. N Engl J Med. 2001 Jun 28;344(26):1959-65 - PubMed
  27. J Clin Invest. 1995 Sep;96(3):1631-8 - PubMed
  28. Am J Respir Crit Care Med. 1999 Jan;159(1):220-7 - PubMed
  29. Am J Cardiol. 2001 Mar 15;87(6):815-8, A9 - PubMed
  30. Arthritis Rheum. 1999 Dec;42(12):2561-8 - PubMed
  31. In Vitro. 1981 Sep;17(9):777-85 - PubMed
  32. Carcinogenesis. 2005 May;26(5):883-91 - PubMed
  33. Lancet. 2004 Jun 19;363(9426):2015-21 - PubMed
  34. Clin Cancer Res. 2001 Jul;7(7):2067-75 - PubMed

Publication Types