- 作者: Kou-Gi Shyu; Su-Kiat Chua; Bao-Wei Wang; Peiliang Kuan
- 作者服務機構: Division of Cardiology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan, R.O.C.
- 中文摘要: --
- 英文摘要:
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-α (TNF-α) stimulation in cultured
macrophages. Cultured macrophages were obtained from human peripheral blood
mononuclear cells. TNF-α stimulation increased resistin protein and mRNA
expression and atorvastatin inhibited the induction of resistin by TNF-α. Addition of
mevalonate induced resistin protein expression similar to TNF-α 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-α and mevalonate. TNF-α
induced phosphorylation of Rac, while atorvastatin and Rac-1 inhibitor inhibited the
phosphorylation of Rac induced by TNF-α. The gel shift and promoter activity
assay showed that TNF-α 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-α. Recombinant resistin and TNF-α
significantly reduced glucose uptake in cultured macrophages, while atorvastatin
3
reversed the reduced glucose uptake by TNF-α. In conclusion, JNK and Rac pathway
mediates the inhibitory effect of atorvastatin on resistin expression induced by
TNF-α. - 中文關鍵字: --
- 英文關鍵字: --