Curcumin prevents lipopolysaccharide-induced matrix metalloproteinase-2 activity via the Ras/MEK1/2 signaling pathway in rat vascular smooth muscle cells

Abstract

The aim of the present study was to examine the effect of curcumin treatment on lipopolysaccharide (LPS)-induced matrix metalloproteinase-2 (MMP-2) activity, and assess whether the effects are mediated by the Ras/mitogen-activated protein kinase kinase 1/2 (MEK1/2) signaling pathway in vascular smooth muscle cells (VSMCs). VSMCs were isolated from male Sprague-Dawley rats. Protein expression levels were analyzed by western blotting. The activity of MMP-2 was measured with gelatin zymography, and an electrophoretic mobility shift assay was used to detect the DNA binding activity of nuclear factor-κB (NF-κB). Curcumin treatment was demonstrated to inhibit LPS-induced MMP-2 activity in rat VSMCs. This inhibitory effect was partially blocked by ammonium pyrrolidinedithiocarbamate, an inhibitor of NF-κB activation, and farnesylthiosalicylic acid, an inhibitor of Ras. In addition, the results of the present study indicated that LPS-induced phosphorylation of Ras homolog family member A and MEK1/2 was significantly decreased by curcumin. Furthermore, NF-κB p65 expression in the nucleus and the DNA binding activity of NF-κB in rat LPS-exposed VSMCs was decreased by curcumin. Taken together, these findings suggest that curcumin prevents of LPS-induced MMP-2 activity through Ras/MEK1/2 and NF-κB signaling.