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Simvastatin induces apoptosis of fibroblast-like synoviocytes.

Litinsky I, Golan I, Yaron M, Yaron I, Caspi D, Elkayam O - Open Rheumatol J (2009)

Bottom Line: To evaluate the effect of varying doses of simvastatin on apoptosis of FLS.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.Varying concentrations of simvastatin induce apoptosis of activated fibroblast-like synoviocytes, suggesting another possible mechanism of anti-inflammatory effects of statins in inflammatory conditions.

View Article: PubMed Central - PubMed

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

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.

No MeSH data available.


Related in: MedlinePlus

The levels of apoptosis of human fibroblasts activated by LPS, treated with different doses of simvastatin. A dose dependent apoptosis of FLS can be observed: the level of apoptosis under 1 mcmol/ml is similar to untreated cells while 15 mcrmo/ml of simvastatin induce apoptosis of more than 48 %.Dose-dependent effects of simvastatin on the levels of apoptosis of human fibroblasts-like synoviocytes in the medium of synovial culture activated by LPS (3µg/ml). The proportion of apoptosis of activated human fibroblasts-like synoviocytes was measured after 48 hours incubation with different doses of simvastatin: (A) Simvastatin 1 µmol/ml; (B) Simvastatin 5 µmol/ml; (C) Simvastatin 15 µmol/ml; (D) Simvastatin 50 µmol/ml.
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Figure 2: The levels of apoptosis of human fibroblasts activated by LPS, treated with different doses of simvastatin. A dose dependent apoptosis of FLS can be observed: the level of apoptosis under 1 mcmol/ml is similar to untreated cells while 15 mcrmo/ml of simvastatin induce apoptosis of more than 48 %.Dose-dependent effects of simvastatin on the levels of apoptosis of human fibroblasts-like synoviocytes in the medium of synovial culture activated by LPS (3µg/ml). The proportion of apoptosis of activated human fibroblasts-like synoviocytes was measured after 48 hours incubation with different doses of simvastatin: (A) Simvastatin 1 µmol/ml; (B) Simvastatin 5 µmol/ml; (C) Simvastatin 15 µmol/ml; (D) Simvastatin 50 µmol/ml.

Mentions: Simvastatin induced apoptosis of human fibroblasts in a dose dependent manner. The proportion of apoptotic cells of resting or activated human fibroblasts lipopolysaccharide (LPS; 3μg/ml) not treated with simvastatin was 21% (Fig. 1). At 48 hours, the proportion of apoptosis of fibroblasts activated by LPS and incubated with 1, 5, 15 and 50 μmol/ml was 22%, 32%, 48% and 41% respectively (Fig. 2).


Simvastatin induces apoptosis of fibroblast-like synoviocytes.

Litinsky I, Golan I, Yaron M, Yaron I, Caspi D, Elkayam O - Open Rheumatol J (2009)

The levels of apoptosis of human fibroblasts activated by LPS, treated with different doses of simvastatin. A dose dependent apoptosis of FLS can be observed: the level of apoptosis under 1 mcmol/ml is similar to untreated cells while 15 mcrmo/ml of simvastatin induce apoptosis of more than 48 %.Dose-dependent effects of simvastatin on the levels of apoptosis of human fibroblasts-like synoviocytes in the medium of synovial culture activated by LPS (3µg/ml). The proportion of apoptosis of activated human fibroblasts-like synoviocytes was measured after 48 hours incubation with different doses of simvastatin: (A) Simvastatin 1 µmol/ml; (B) Simvastatin 5 µmol/ml; (C) Simvastatin 15 µmol/ml; (D) Simvastatin 50 µmol/ml.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2746119&req=5

Figure 2: The levels of apoptosis of human fibroblasts activated by LPS, treated with different doses of simvastatin. A dose dependent apoptosis of FLS can be observed: the level of apoptosis under 1 mcmol/ml is similar to untreated cells while 15 mcrmo/ml of simvastatin induce apoptosis of more than 48 %.Dose-dependent effects of simvastatin on the levels of apoptosis of human fibroblasts-like synoviocytes in the medium of synovial culture activated by LPS (3µg/ml). The proportion of apoptosis of activated human fibroblasts-like synoviocytes was measured after 48 hours incubation with different doses of simvastatin: (A) Simvastatin 1 µmol/ml; (B) Simvastatin 5 µmol/ml; (C) Simvastatin 15 µmol/ml; (D) Simvastatin 50 µmol/ml.
Mentions: Simvastatin induced apoptosis of human fibroblasts in a dose dependent manner. The proportion of apoptotic cells of resting or activated human fibroblasts lipopolysaccharide (LPS; 3μg/ml) not treated with simvastatin was 21% (Fig. 1). At 48 hours, the proportion of apoptosis of fibroblasts activated by LPS and incubated with 1, 5, 15 and 50 μmol/ml was 22%, 32%, 48% and 41% respectively (Fig. 2).

Bottom Line: To evaluate the effect of varying doses of simvastatin on apoptosis of FLS.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.Varying concentrations of simvastatin induce apoptosis of activated fibroblast-like synoviocytes, suggesting another possible mechanism of anti-inflammatory effects of statins in inflammatory conditions.

View Article: PubMed Central - PubMed

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

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.

No MeSH data available.


Related in: MedlinePlus