Effects of ERK by TNF-α in deciduous dental pulp fibroblasts

Inflammation in dental pulp tissue is associated with tissue degradation, and matrix metalloproteinases (MMPs) are believed to participate in this destruction. Elevated levels of some MMPs have been reported in inflamed pulp and periapical lesions. Moreover, in inflamed pulp, many kinds of inflammatory cytokines such as interleukin (IL)-1β and tumor necrosis factor (TNF)-α, are released from inflammatory cells like macrophages, lymphocytes and neutrophils. In the present study, we examined whether TNF-α affected the production of MMP-2 in deciduous dental pulp fibroblasts and its signaling pathways utilizing gelatin zymography and western blotting analysis. TNF-α increased the expression of MMP-2 in a dose-dependent manner in deciduous dental pulp fibroblasts. U0126, which are MEK1/2 inhibitors, inhibited the MMP-2 production induced by TNF-α in deciduous dental pulp fibroblasts. Moreover, in deciduous dental pulp fibroblasts cultured with TNF-α, ERK1/2 was phosphorylated in a time-dependent manner with the maximum phosphorylation at 30 min, and U0126 abolished this phosphorylation of MEK1/2 in TNF-α-stimulated deciduous dental pulp fibroblasts. These results suggest that TNF-α may enhance pulp tissue destruction during pulp inflammation in part by regulating MMP-2, and that the MEK1/2-ERK1/2 pathway is involved in MMP-2 production in deciduous dental pulp fibroblasts.