Simvastatin inhibits NF-κB signaling in intestinal epithelial cells and ameliorates acute murine colitis

Statins, HMG-CoA reductase inhibitors exert pleiotropic anti-inflammatory properties in vitro and in vivo, and are associated with the risk reduction of colorectal cancer. It remains unknown, however, whether statin is effective for the treatment of inflammatory bowel disease (IBD). Therefore, we investigated anti-inflammatory effects of simvastatin on intestinal epithelial cells (IEC) and on an experimental murine colitis model, and elucidated its molecular mechanisms. Simvastatin (50 mu M) significantly inhibited TNF-alpha-induced IL-8 gene expression in COLO 205 cells. Simvastatin (50 mu M) blocked TNF-alpha-induced NF-KB transcriptional activity, IKB phosphorylation/degradation and DNA binding activity of NF-KB. Administration of simvastatin significantly reduced the severity of dextran sulfate sodium (DSS)-induced murine colitis as assessed by body weight, colon length, DAI, and histology in a dose-dependent manner. These results suggest that simvastatin inhibits proinflammatory gene expression by blocking NF-KB signaling in IEC, and attenuates DSS-induced acute murine colitis. Simvastatin could be a potential agent for the treatment of IBD. (c) 2006 Elsevier B.V. All rights reserved.