Atorvastatin activates PPAR-gamma 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.


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.
Grip
O
O
Department of Medicine, Lund University, University Hospital MAS, Malmö, Sweden. olof.grip@medforsk.mas.lu.se
Janciauskiene
S
S
Lindgren
S
S
D000924:Anticholesteremic Agents / Q000494:pharmacology*; D000069059:Atorvastatin; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000517:prevention & control*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology; D010101:Oxygen Consumption / Q000187:drug effects; D011758:Pyrroles / Q000494:pharmacology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000924:Anticholesteremic Agents; D018932:Chemokine CCL2; D006538:Heptanoic Acids; D011758:Pyrroles; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D000069059:Atorvastatin; D020780:Matrix Metalloproteinase 9