Atorvastatin activates PPAR-γ and attenuates the inflammatory response in human monocytes

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 mumol/l) 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.