title: Rosuvastatin suppresses the inflammatory responses through inhibition of c-Jun N-terminal kinase and Nuclear Factor-kappaB in endothelial cells.
abstract: 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)-alpha (10 ng/mL) alone or with rosuvastatin (100 microM). 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-kappaB) was determined by Western blot.
  
  
  RESULTS
  Rosuvastatin decreased the extent of U937 adhesion to TNF-alpha-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-kappaB was also blocked by rosuvastatin. The inhibitors of JNK, NF-kappaB, and STAT-3 produced a statistically significant decrease of the TNF-alpha 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-kappaB.
authors.affiliation: The Heart Center of Chonnam National University Hospital, Gwangju, South Korea.
authors.forename: Yong Sook
authors.initials: YS
authors.lastname: Kim
authors.forename: Youngkeun
authors.initials: Y
authors.lastname: Ahn
authors.forename: Moon Hwa
authors.initials: MH
authors.lastname: Hong
authors.forename: Kye Hun
authors.initials: KH
authors.lastname: Kim
authors.forename: Hyung Wook
authors.initials: HW
authors.lastname: Park
authors.forename: Young Joon
authors.initials: YJ
authors.lastname: Hong
authors.forename: Ju Han
authors.initials: JH
authors.lastname: Kim
authors.forename: Weon
authors.initials: W
authors.lastname: Kim
authors.forename: Myung Ho
authors.initials: MH
authors.lastname: Jeong
authors.forename: Jeong Gwan
authors.initials: JG
authors.lastname: Cho
authors.forename: Jong Chun
authors.initials: JC
authors.lastname: Park
authors.forename: Jung Chaee
authors.initials: JC
authors.lastname: Kang
mesh_terms: D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D018929:Cell Culture Techniques; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D042783:Endothelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005464:Fluorobenzenes / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D008798:Mevalonic Acid / Q000494:pharmacology; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D010766:Phosphorylation; D011743:Pyrimidines / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000068718:Rosuvastatin Calcium; D050796:STAT3 Transcription Factor / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D020298:U937 Cells
chemical_list: D016207:Cytokines; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D016328:NF-kappa B; D011743:Pyrimidines; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; D000068718:Rosuvastatin Calcium; D048031:JNK Mitogen-Activated Protein Kinases; D008798:Mevalonic Acid