Lovastatin and mevastatin reduce basal and cytokine-stimulated production of prostaglandins from rat microglial cells in vitro: evidence for a mechanism unrelated to the inhibition of hydroxy-methyl-glutaryl CoA reductase.
Statins were recently shown to possess anti-inflammatory activities, which might be responsible for their favourable effects in cardiovascular or CNS disorders independently from the inhibition of hydroxy-methyl-glutaryl CoA reductase. Here we investigated the effects of the statins lovastatin and mevastatin on prostanoid production in primary cultures of rat cortical microglia and astrocytes. We found that both statins significantly reduce prostaglandin E2 (PGE2) release from microglia, either under basal conditions or after stimulation by interleukin-1beta. Lovastatin also tends to reduce, although not in a significant manner, basal and interleukin-1beta-stimulated PGE2 release from astrocytes. Precursors and intermediates in cholesterol biosynthesis--mevalonic acid and geranyl and farnesyl pyrophosphate--also reduce PGE2 production, and potentiate the inhibitory effects of statins, suggesting that the latter might not depend on the inhibition of hydroxy-methyl-glutaryl CoA reductase.
Tringali
Giuseppe
G
Institute of Pharmacology, Catholic University Medical School, Largo Francesco Vito 1, 00168 Rome, Italy.
Vairano
Mauro
M
Dello Russo
Cinzia
C
Preziosi
Paolo
P
Navarra
Pierluigi
P
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020274:Autoimmune Diseases of the Nervous System / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000187:drug effects* / Q000378:metabolism; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004357:Drug Synergism; D004660:Encephalitis / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D008798:Mevalonic Acid / Q000378:metabolism / Q000494:pharmacology; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011106:Polyisoprenyl Phosphates / Q000378:metabolism / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism*; D051381:Rats; D012717:Sesquiterpenes
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007375:Interleukin-1; D011106:Polyisoprenyl Phosphates; D011453:Prostaglandins; D012717:Sesquiterpenes; C012258:mevastatin; C015234:geranyl pyrophosphate; C004808:farnesyl pyrophosphate; D008148:Lovastatin; D006903:Hydroxymethylglutaryl CoA Reductases; D015232:Dinoprostone; D008798:Mevalonic Acid