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

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Abstract
To investigate the ability of statins to activate the nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-γ) in primary human monocytes in culture. Human peripheral monocytes were incubated with atorvastatin (0.1–10 μmol/l) for up to 24 hours. PPAR-γ 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. We found that atorvastatin activates PPAR-γ 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 %. 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.