Simvastatin affects cell motility and actin cytoskeleton distribution of microglia.
Statin treatment is proposed to be a new potential therapy for multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system. The effects of statin treatment on brain cells, however, are hardly understood. We therefore evaluated the effects of simvastatin treatment on the migratory capacity of brain microglial cells, key elements in the pathogenesis of MS. It is shown that exposure of human and murine microglial cells to simvastatin reduced cell surface expression of the chemokine receptors CCR5 and CXCR3. In addition, simvastatin treatment specifically abolished chemokine-induced microglial cell motility, altered actin cytoskeleton distribution, and led to changes in intracellular vesicles. These data clearly show that simvastatin inhibits several immunological properties of microglia, which may provide a rationale for statin treatment in MS.
Kuipers
Hedwich F
HF
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
Rappert
Angelika A C
AA
Mommaas
A Mieke
AM
van Haastert
Elise S
ES
van der Valk
Paul
P
Boddeke
Hendrikus W G M
HW
Biber
Knut P H
KP
van den Elsen
Peter J
PJ
D000199:Actins / Q000378:metabolism*; D000818:Animals; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects; D005434:Flow Cytometry; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D019713:Receptors, CCR5 / Q000096:biosynthesis / Q000235:genetics; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000235:genetics; D018121:Receptors, Cytokine / Q000096:biosynthesis / Q000187:drug effects; D019821:Simvastatin / Q000494:pharmacology*
D000199:Actins; C515187:CXCR3 protein, human; C515188:Cxcr3 protein, mouse; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019713:Receptors, CCR5; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D002784:Cholesterol; D019821:Simvastatin