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

Research output: Contribution to journalArticle

21 Citations (Scopus)

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-.

Original languageEnglish
Article number50
JournalJournal of Biomedical Science
Volume16
Issue number1
DOIs
Publication statusPublished - 2009

Fingerprint

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)

Cite this

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.

In: Journal of Biomedical Science, Vol. 16, No. 1, 50, 2009.

Research output: Contribution to journalArticle

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