Mechanism of inhibitory effect of atorvastatin on resistin expression induced by tumor necrosis factor- in macrophages

Kou Gi Shyu, Su Kiat Chua, Bao Wai Wang, Peiliang Kuan

研究成果: 雜誌貢獻文章

21 引文 (Scopus)

摘要

Atorvastatin has been shown to reduce resistin expression in macrophages after pro-inflammatory stimulation. However, the mechanism of reducing resistin expression by atorvastatin is not known. Therefore, we sought to investigate the molecular mechanisms of atorvastatin for reducing resistin expression after proinflammatory cytokine, tumor necrosis factor- (TNF-) stimulation in cultured macrophages. Cultured macrophages were obtained from human peripheral blood mononuclear cells. TNF- stimulation increased resistin protein and mRNA expression and atorvastatin inhibited the induction of resistin by TNF-. Addition of mevalonate induced resistin protein expression similar to TNF- stimulation. However, atorvastatin did not have effect on resistin protein expression induced by mevalonate. SP600125 and JNK small interfering RNA (siRNA) completely attenuated the resistin protein expression induced by TNF- and mevalonate. TNF- induced phosphorylation of Rac, while atorvastatin and Rac-1 inhibitor inhibited the phosphorylation of Rac induced by TNF-. The gel shift and promoter activity assay showed that TNF- increased AP-1-binding activity and resistin promoter activity, while SP600125 and atorvastatin inhibited the AP-1-binding activity and resistin promoter activity induced by TNF-. Recombinant resistin and TNF- significantly reduced glucose uptake in cultured macrophages, while atorvastatin reversed the reduced glucose uptake by TNF-. In conclusion, JNK and Rac pathway mediates the inhibitory effect of atorvastatin on resistin expression induced by TNF-.
原文英語
文章編號50
期刊Journal of Biomedical Science
16
發行號1
DOIs
出版狀態已發佈 - 2009

指紋

Resistin
Macrophages
Tumor Necrosis Factor-alpha
Mevalonic Acid
Phosphorylation
Transcription Factor AP-1
Atorvastatin Calcium
Proteins
Glucose
MAP Kinase Signaling System
Small Interfering RNA
Assays
Blood Cells

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Cell Biology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism
  • Pharmacology (medical)

引用此文

Mechanism of inhibitory effect of atorvastatin on resistin expression induced by tumor necrosis factor- in macrophages. / Shyu, Kou Gi; Chua, Su Kiat; Wang, Bao Wai; Kuan, Peiliang.

於: Journal of Biomedical Science, 卷 16, 編號 1, 50, 2009.

研究成果: 雜誌貢獻文章

Shyu, Kou Gi ; Chua, Su Kiat ; Wang, Bao Wai ; Kuan, Peiliang. / Mechanism of inhibitory effect of atorvastatin on resistin expression induced by tumor necrosis factor- in macrophages. 於: Journal of Biomedical Science. 2009 ; 卷 16, 編號 1.
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abstract = "Atorvastatin has been shown to reduce resistin expression in macrophages after pro-inflammatory stimulation. However, the mechanism of reducing resistin expression by atorvastatin is not known. Therefore, we sought to investigate the molecular mechanisms of atorvastatin for reducing resistin expression after proinflammatory cytokine, tumor necrosis factor- (TNF-) stimulation in cultured macrophages. Cultured macrophages were obtained from human peripheral blood mononuclear cells. TNF- stimulation increased resistin protein and mRNA expression and atorvastatin inhibited the induction of resistin by TNF-. Addition of mevalonate induced resistin protein expression similar to TNF- stimulation. However, atorvastatin did not have effect on resistin protein expression induced by mevalonate. SP600125 and JNK small interfering RNA (siRNA) completely attenuated the resistin protein expression induced by TNF- and mevalonate. TNF- induced phosphorylation of Rac, while atorvastatin and Rac-1 inhibitor inhibited the phosphorylation of Rac induced by TNF-. The gel shift and promoter activity assay showed that TNF- increased AP-1-binding activity and resistin promoter activity, while SP600125 and atorvastatin inhibited the AP-1-binding activity and resistin promoter activity induced by TNF-. Recombinant resistin and TNF- significantly reduced glucose uptake in cultured macrophages, while atorvastatin reversed the reduced glucose uptake by TNF-. In conclusion, JNK and Rac pathway mediates the inhibitory effect of atorvastatin on resistin expression induced by TNF-.",
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