Pharmacological inhibitors of the mevalonate pathway activate pro-IL-1 processing and IL-1 release by human monocytes

• Published in: European cytokine network Vol. 20; no. 3; p. 112
• Main Authors: Massonnet, Benoit, Normand, Sylvain, Moschitz, Reinhard, Delwail, Adriana, Favot, Laure, Garcia, Martine, Bourmeyster, Nicolas, Cuisset, Laurence, Grateau, Gilles, Morel, Franck, Silvain, Christine, Lecron, Jean-Claude
• Format: Journal Article
• Language: English
• Published: France 01.09.2009
• Subjects: Caspase 1 - metabolism; Cell Line; Enzyme Activation - drug effects; Guanosine Triphosphate - metabolism; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology; Interleukin-1 - secretion; Interleukin-1beta - secretion; Lipopolysaccharides - pharmacology; Metabolic Networks and Pathways - drug effects; Mevalonic Acid - metabolism; Monocytes - drug effects; Monocytes - enzymology; Monocytes - secretion; p38 Mitogen-Activated Protein Kinases - metabolism; Phosphorylation - drug effects; Protein Precursors - secretion; Protein Prenylation - drug effects; Protein Processing, Post-Translational - drug effects; Protein Transport - drug effects; rac1 GTP-Binding Protein - metabolism; Simvastatin - pharmacology

The effects of statins (3-hydroxy-3-methylglutaryl coenzyme A reductase-HMGR-inhibitors) on the inflammatory response remain unclear. HMGR is implicated in the mevalonate pathway, directly upstream of cholesterol biosynthesis. We studied the impairment by this pathway of cytokine production by perip...