IL-1β-induced MCP-1 expression and secretion of human dental pulp cells is related to TAK1, MEK/ERK, and PI3K/Akt signaling pathways

• IL-1β stimulated MCP-1 mRNA, protein expression and its secretion of pulp cells.
• IL-1β-induced MCP-1 expression is attenuated by TAK1, MEK/ERK and PI3K/Akt inhibitors.
• IL-1β-induced MCP-1 secretion is attenuated by TAK1, MEK/ERK and PI3K/Akt inhibitors.
• IL-1β plays crucial role in pulpal inflammation by stimulation of MCP-1.
• TAK1, MEK/ERK and PI3K/Akt are involved in these events.

ObjectiveInterleukin-1β (IL-1β) is an inflammatory molecule of the dental pulp. IL-1β stimulates cyclooxygenase-2 (COX-2) and prostaglandins production of pulp cells and affects the pulpal inflammation and repair. However, the effects of IL-1β on Monocyte Chemotactic Factor-1 (MCP-1) of dental pulp cells and its relation to transforming growth factor β-activated kinase-1 (TAK1), PI3K/Akt, and MEK/ERK signaling and COX activation are not fully clear.DesignHuman dental pulp cells were exposed to IL-1β with/without pretreatment and co-incubation by aspirin (a COX inhibitor), 5z-7-oxozeaenol (a TAK1 inhibitor), LY294002 (a PI3K/Akt inhibitor) or U0126 (a MEK/ERK inhibitor). Viable cell number was evaluated by MTT assay. MCP-1 mRNA expression was tested by reverse transcriptase-polymerase chain reaction (RT-PCR). MCP-1 and COX-2 protein expression was studied by western blot. MCP-1 in the culture medium was measure by ELISA.ResultsIL-1β showed little cytotoxicity to pulp cells. It stimulated MCP-1 mRNA and protein expression and MCP-1 secretion. Aspirin, U0126, LY294002 and 5z-7-oxozeaenol attenuated the IL-1β-induced MCP-1 expression. In addition, 5z-7-oxozeaenol, LY294002, U0126 and aspirin prevented the IL-1β-induced MCP-1 secretion of pulp cells.ConclusionThese results indicate that IL-1β may be involved in the pulpal inflammatory and healing processes by inducing MCP-1 expression and secretion. These events are related to differential activation of TAK1, PI3K/Akt and MEK/ERK 1/2 signaling and COX activation. These results are important for future pharmacologic intervention of pulpal inflammatory diseases.