SOD2 is upregulated in periodontitis to reduce further inflammation progression.

OBJECTIVES: Periodontitis is a highly prevalent chronic inflammatory disease that results in destruction of tooth-supporting structures followed by tooth-loss. Until now, periodontitis has been regarded to be initiated by bacterial infection followed by aberrant host response. Although increasing evidence suggests a strong association between oxidative stress and periodontitis, precise molecular mechanism has been left unanswered. In this study, we investigated roles of SOD2, the main antioxidant enzyme maintaining reactive oxygen species (ROS) homeostasis, under inflammatory conditions. METHODS: We computationally analyzed SOD2 expression in periodontitis. To confirm this data, immunoblot assay was performed with samples from periodontitis patients. The cellular mechanism of change in SOD2 expression was identified through immunoblot assay and immunofluorescence. To evaluate the molecular function of SOD2, we generated SOD2-deficient cells by utilizing the CRISPR/Cas9 system. RESULTS: We first determined that SOD2 expression was significantly increased in periodontitis. We also confirmed that SOD2 expression was upregulated through the NF-kappaB pathway when the inflammatory signal was stronger and extended. Gene manipulation against SOD2 through the CRISPR/Cas9 system showed that the absence of SOD2 increased production of NLRP3 inflammasome components. CONCLUSIONS: Our study demonstrates that intracellular SOD2 has a protective role by suppressing NLRP inflammasome-caspase-1-IL-1beta axis under inflammatory conditions.