Rosuvastatin Suppresses the Inflammatory Responses Through Inhibition of c-Jun N-terminal Kinase and Nuclear Factor-κB in Endothelial Cells

BACKGROUND:Rosuvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, has pleiotropic effects that are anti-inflammatory and antiatherothrombotic. It is important to understand the cardioprotective effects of rosuvastatin in order to optimize its additional advantages in the treatment and prevention of cardiovascular diseases. METHODS:Human umbilical vein endothelial cells (HUVEC) were treated with tumor necrosis factor (TNF)-α (10 ng/mL) alone or with rosuvastatin (100 μM). The extent of inflammation was determined by U937 adhesion assay as well as analysis of the expression of intercellular adhesion molecule (ICAM)-1, monocyte chemoattractant protein (MCP)-1, interleukin (IL)-8, IL-6, cyclooxygenase (COX)-2, c-Jun N-terminal kinase (JNK), extracellular signal-regulated protein kinase (ERK), p38, and signal transducer and activator of transcription (STAT)-3. The activation of nuclear factor kappa B (NF-κB) was determined by Western blot. RESULTS:Rosuvastatin decreased the extent of U937 adhesion to TNF-α-stimulated HUVEC. Rosuvastatin inhibited the expressions of ICAM-1, MCP-1, IL-8, IL-6, and COX-2 mRNA and protein levels. The activation of JNK and NF-κB was also blocked by rosuvastatin. The inhibitors of JNK, NF-κB, and STAT-3 produced a statistically significant decrease of the TNF-α induced U937 adhesion and IL-6 protein release. CONCLUSIONS:This study suggests that the anti-inflammatory activity of rosuvastatin is accompanied by the inhibition of JNK and NF-κB.