Curcumin suppresses tumor necrosis factor-α-induced matrix metalloproteinase-2 expression and activity in rat vascular smooth muscle cells via the NF-κB pathway.

Abstract

The aim of the present study was to investigate the inhibitory effect of curcumin on tumor necrosis factor (TNF)-α-induced cell migration and matrix metalloproteinase (MMP)-2 expression and activity in rat vascular smooth muscle cells (VSMCs), in order to identify whether the effects are mediated by the nuclear factor (NF)-κB signaling pathway. The VSMCs cells were pretreated with curcumin prior to stimulation with TNF-α. Reverse transcription-polymerase chain reaction and western blot analysis were used to determine the MMP-2 mRNA and protein expression levels in TNF-α-stimulated VSMCs. Activity levels of MMP-2 were measured using a gelatin zymography assay. Intracellular reactive oxygen species (ROS) generation was also analyzed. Curcumin was found to suppress the TNF-α-stimulated migration of VSMCs. In addition, curcumin inhibited the TNF-α-induced induction of MMP-2 activity and expression. Curcumin also decreased ROS generation in TNF-α-stimulated VSMCs. Signal transduction experiments indicated that TNF-α-induced MMP-2 expression in VSMCs was partly reversed with the application of an NF-κB inhibitor (BAY11-7082). In addition, western blot analysis revealed that curcumin reduced NF-κB p65 protein expression in TNF-α-stimulated VSMCs at the concentration of 20 and 40 μM. Therefore, these observations indicated that curcumin suppressed TNF-α-stimulated VSMC migration and partially prevented TNF-α-induced MMP-2 expression and activity in VSMCs via the NF-κB pathway.