Lovastatin Inhibits Proliferation and Differentiation and Causes Apoptosis in Lipopolysaccharide-Stimulated Murine B Cells

Lipopolysaccharide-stimulated murine B lymphocytes were incubated with the pharmacologic drug lovastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase at concentrations ranging from 10 −5-10 −8M. After 48 hr, treatment with 10 −5M lovastatin inhibited [ 3H] thymidine in...

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Veröffentlicht in:Biochemical and biophysical research communications 1995-06, Vol.211 (2), p.665-670
Hauptverfasser: Reedquist, K.A., Pope, T.K., Roess, D.A.
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container_title Biochemical and biophysical research communications
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creator Reedquist, K.A.
Pope, T.K.
Roess, D.A.
description Lipopolysaccharide-stimulated murine B lymphocytes were incubated with the pharmacologic drug lovastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase at concentrations ranging from 10 −5-10 −8M. After 48 hr, treatment with 10 −5M lovastatin inhibited [ 3H] thymidine incorporation 55%. Flow cytometric analysis indicated that the fraction of B cells in S phase was reduced from 26.7% ± 5.44% to 11.6% ± 2.9% when cells were incubated with 10 −5M lovastatin. In addition, a large peak appeared to the left of the G 1 peak that was indicative of apoptosis in cells treated with 10 −5M lovastatin. At 96 hr, the number of plaque-forming B cells was decreased 50% in the presence of lovastatin. Together these results suggest that high concentrations of lovastatin can inhibit B cell proliferation and differentiation of murine B lymphocytes in lipopolysaccharide-activated B cells, perhaps through induction of programmed cell death.
doi_str_mv 10.1006/bbrc.1995.1863
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subjects Animals
Apoptosis - drug effects
B-Lymphocytes - cytology
B-Lymphocytes - drug effects
B-Lymphocytes - physiology
Cell Cycle - drug effects
Cell Differentiation - drug effects
Cell Division - drug effects
Cells, Cultured
DNA - biosynthesis
DNA - drug effects
Flow Cytometry
Hemolytic Plaque Technique
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Lipopolysaccharides - pharmacology
Lovastatin - pharmacology
Lymphocyte Activation - drug effects
Lymphocyte Depletion
Mice
Spleen - immunology
T-Lymphocytes
Thymidine - metabolism
title Lovastatin Inhibits Proliferation and Differentiation and Causes Apoptosis in Lipopolysaccharide-Stimulated Murine B Cells
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