Involvement of peroxisome proliferator activated receptor in the anti-inflammatory effects of atorvastatin in oxygen-glucose deprivation/reperfusion-stimulated RAW264.7 murine macrophages

Abstract

Ischemia reperfusion (I/R) injury is important in the pathogenesis and/or progression of various diseases, including stroke, cardiovascular disease and acute renal injury. Increasing evidence indicates that atorvastatin exerts protective effects in I/R injury associated diseases; however, the underlying mechanisms remain to be fully elucidated. In the present study, oxygen glucose deprivation (OGD)/reperfusion stimulated. RAW264.7 murine macrophages served as a model of I/R injury. The knockdown of peroxisome proliferator activated receptor (PPAR) expression in these cells increased OGD/reperfusion induced expression of inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF) and interferon (IFN), and enhanced OGD/reperfusion induced downregulation of the expression of cluster of differentiation (CD) 206, at the mRNA and protein levels. Conversely, overexpression of PPAR significantly attenuated OGD/reperfusioninduced alterations in the expression of iNOS, TNF, IFN and CD206 at the mRNA and protein levels. Notably, atorvastatin inhibited OGD/reperfusioninduced iNOS expression and reversed OGD/reperfusioninduced downregulation of the expression of CD206 and PPAR at the mRNA and protein levels. The results of the present study indicate that atorvastatin exhibits significant antiinflammatory effects in OGD/reperfusionstimulated RAW264.7 cells, possibly via PPAR regulation. The findings of the present study may reveal a novel mechanism underlying the protective effects of atorvastatin in I/R injuryassociated diseases.