Pravastatin inhibits pro-inflammatory effects of Alzheimer's peptide Abeta(1-42) in glioma cell culture in vitro.
Statins are known to exert a number of biological effects apart from reducing cholesterol synthesis. The results of recent studies indicate that patients treated with pravastatin have a lower prevalence of diagnosed Alzheimer's disease (AD). These observations prompted us to examine the effects of pravastatin on Alzheimer's peptide (Abeta(1-42))-induced pro-inflammatory activation in the human glioma cell line in vitro. Cells alone or cells pre-treated with pravastatin (0.1mg x ml(-1)) for 24h were stimulated with 5 microM of freshly dissolved Abeta(1-42) for the next 24h. The pre-treatment of cells with pravastatin diminished the capacity of Abeta to induce metalloproteinases, cytokine IL-6 and free radical levels. Although both pravastatin and Abeta(1-42) separately increased PPARgamma activity, the combination of Abeta(1-42) and pravastatin resulted in no effect on PPARgamma expression. These data indicate that soluble forms of Abeta(1-42), which are a potent stimulus of pro-inflammatory activation of glioma cells in vitro, could be a good target for pravastatin.
Sun
Yong-Xin
YX
Department of Medicine, University Hospital Malmö, Ing 46, UMAS, S-20502, Malmö, Sweden.
Crisby
Milita
M
Lindgren
Stefan
S
Janciauskiene
Sabina
S
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D001932:Brain Neoplasms / Q000473:pathology*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D003124:Colorimetry; D016207:Cytokines / Q000096:biosynthesis; D004591:Electrophoresis, Polyacrylamide Gel; D024202:Electrophoretic Mobility Shift Assay; D005609:Free Radicals / Q000378:metabolism; D005910:Glioma / Q000473:pathology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007249:Inflammation / Q000139:chemically induced* / Q000517:prevention & control*; D015227:Lipid Peroxidation / Q000187:drug effects; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D008666:Metalloendopeptidases / Q000378:metabolism; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D017035:Pravastatin / Q000494:pharmacology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014407:Tumor Cells, Cultured
D016229:Amyloid beta-Peptides; D016207:Cytokines; D005609:Free Radicals; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010446:Peptide Fragments; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; C075222:amyloid beta-protein (1-42); D008666:Metalloendopeptidases; D020780:Matrix Metalloproteinase 9; D017035:Pravastatin