MECHANICAL STRESS INDUCED IL-1β RELEASE IN HPDL CELLS VIA PANNEXIN-1/P2X7R

Introduction: Mechanical stress is one of the factors involved in the homeostasis of periodontium. Previous studies showed mechanical stress induced expression of osteopontin and RANKL through the release of ATP in human periodontal ligament (HPDL) cells. Objective: The aim of this study was to investigate the effect of mechanical stress on the expression of inflammatory cytokines. Material and Methods: Mechanical stress was generated by direct loading of weight on the culture of HPDL cells. Inflammatory cytokine expression was examined by reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). The molecular mechanism of stress-induced cytokine expression was investigated by means of inhibitors. Results: Mechanical stress induced expression of IL-1β mRNA and proteins, when compared to the control in a force dependent manner. The induction was inhibited by carbenoxolone (non-specific gap junction inhibitor), probenecid (pannexin-1 hemichannel inhibitor), and interestingly by P2X7 receptor (P2X7R) antagonist KN-62. Conclusions: The results from this study indicated that mechanical stress could directly regulate the expression of IL-1β in HPDL cells. The induction involved the function of pannexin-1, and also P2X7 receptor. This finding emphasizes the role of mechanical stress in the regulation of inflammatory cytokine release in periodontal tissue.