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(-8) M. After 48 hr, treatment with 10(-5)M 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(-5)M lovastatin. In addition, a large peak appeared to the left of the G1 peak that was indicative of apoptosis in cells treated with 10(-5)M 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.
Reedquist
K A
KA
Department of Physiology, Colorado State University, Fort Collins 80523, USA.
Pope
T K
TK
Roess
D A
DA
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D002453:Cell Cycle / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D005434:Flow Cytometry; D006462:Hemolytic Plaque Technique; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008148:Lovastatin / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008212:Lymphocyte Depletion; D051379:Mice; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes; D013936:Thymidine / Q000378:metabolism
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008070:Lipopolysaccharides; D004247:DNA; D008148:Lovastatin; D013936:Thymidine