Atorvastatin Activates PPAR-gamma and Attenuates the Inflammatory Response in Human Monocytes

Inflamm Res. 2002 Feb;51(2):58-62. doi: 10.1007/BF02684000.

Abstract

Objective: To investigate the ability of statins to activate the nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-gamma) in primary human monocytes in culture.

Materials and methods: Human peripheral monocytes were incubated with atorvastatin (0.1-10 micromol/1) for up to 24 hours. PPAR-gamma expression was analysed by electrophoretic mobility shift assay. Pro-inflammatory cytokines were measured by enzyme-linked immunosorbent assays, and oxygen consumption was determined polarographically with a Clark-type oxygen electrode.

Results: We found that atorvastatin activates PPAR-gamma and inhibits the production of tumour necrosis factor-alpha up to 38% (p < 0.05), monocyte chemoattractant protein-1 up to 85% (p < 0.05), and gelatinase B up to 73% (p < 0.05), in a concentration-dependent manner. Moreover, atorvastatin shows concentration-dependent inhibition of cellular oxygen consumption up to 41%.

Conclusions: These findings contribute to the growing knowledge of the anti-inflammatory effects of statins, and have led us to the suggestion that statins may control inflammatory responses by the regulation of intracellular lipid homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticholesteremic Agents / pharmacology*
  • Atorvastatin
  • Cell Death / drug effects
  • Cells, Cultured
  • Chemokine CCL2 / metabolism
  • Heptanoic Acids / pharmacology*
  • Humans
  • Inflammation / prevention & control*
  • Matrix Metalloproteinase 9 / metabolism
  • Monocytes / drug effects*
  • Monocytes / physiology
  • Oxygen Consumption / drug effects
  • Pyrroles / pharmacology*
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Transcription Factors / metabolism*
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Anticholesteremic Agents
  • Chemokine CCL2
  • Heptanoic Acids
  • Pyrroles
  • Receptors, Cytoplasmic and Nuclear
  • Transcription Factors
  • Tumor Necrosis Factor-alpha
  • Atorvastatin
  • Matrix Metalloproteinase 9