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

IntroductionThis 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.MethodsROS 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.ResultsHeat 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.ConclusionCollectively, these results show that heat-induced Nrf2 activation is the major regulatory pathway of cytoprotective gene expression against oxidative stress in HDP cells.