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.