Heat Stress Activates Interleukin-8 and the Antioxidant System via Nrf2 Pathways in Human Dental Pulp Cells

Introduction: This study tested whether heat stress (42°C for 30 minutes) induces reactive oxygen species (ROS), proinflammatory cytokines, Nrf2 activation, and Nrf2 target genes such as antioxidant enzymes in human dental pulp (HDP) cells. Methods: ROS was evaluated by using flow cytometry. Proteins and messenger RNA levels for cytokines and antioxidant genes were determined by using Western blotting and reverse transcription-polymerase chain reaction (RT-PCR) analysis, respectively. Results: Heat stress induced the production of ROS and the increased expression of the interleukin (IL)-8 and IL-8 receptor genes. Exposure of cells to heat stress resulted in the nuclear translocation of Nrf2 and increased expression of Nrf2 target genes including heme oxygenase-1. Pretreatment with an exogenous antioxidant inhibited the heat-induced expression of IL-8 and Nrf2 target genes and Nrf2 translocation. Conclusion: Collectively, these results show that heat-induced Nrf2 activation is the major regulatory pathway of cytoprotective gene expression against oxidative stress in HDP cells.