The Involvement of Mitoge-activated Protein Kinases and Transcriptional Factors in Substance P-induced IL-6 Production in Human Dental Pulp Cell Cultures

Abstract

Substance P (SP) induces the expression of proinflammatory cytokines, such as IL-6, which are implicated in pulpal inflammation. We examined whether SP induces IL-6 production using enzymelinked immunosorbent assay (ELISA) in human dental pulp cell (PF-10) cultures. SP induced IL-6 production after 2 h stimulation, and the production remarkably increased after 24 h to 48 h. The SP antagonist L703606 inhibited SP-induced IL-6 production in a dose-dependent manner. Extracellular signal-regulated kinase (ERK) and p38 mitogen-acti-vated protein kinase (MAPK) mediated SP-induced IL-6 production, as shown by the use of specific inhibitors of these kinases. Furthermore, in the siRNA experiments, specific siRNA for activator protein-1 (AP-1) and selective promoter factor 1 (Sp1) inhibited SP-induced IL-6 production. Our results suggest that ERK, p38 MAPK, AP-1, and Sp1 are key factors on the signaling pathway for SP-induced IL-6 production in human dental pulp cells.