IADR Abstract Archives
Zingerone Inhibits Porphyromonas gingivalis-Induced Inflammatory Responses by Activating SIRT1-mediated Autophagy
Objectives: Periodontitis is a chronic inflammatory disease more prevalently found in aged person and is induced by periodontal pathogens including Porphyromonas gingivalis. The expression of SIRT-1, a NAD+-dependent protein deacetylase, is reduced in aged person. Zingerone, a stable active component of dry ginger rhizome, has anti-inflammatory and anti-aging effect. The purpose of this study is to investigate the effects and the action mechanism of zingerone against P. gingivalis- induced inflammation.
Methods: To induce inflammation, bone marrow-derived macrophages (BMDM) and THP-1 cells were infected with P. gingivalis. Protein expression and cytokine production were determined by Western blot and ELISA, respectively. C57BL/6 wild type (WT) and SIRT-1 transgenic mice were challenged with P. gingivalis for the induction of experimental periodontitis. Alveolar bone loss in each mouse was measured by Micro CT.
Results: P. gingivalis infection down-regulated SIRT1 expression and induced IL-1β production in BMDMs. IL-1β production and inflammasome activation were significantly reduced in BMDMs from SIRT-1 transgenic mice compared to the WT mice. Bone resorption was inhibited in SIRT1 transgenic mice compared to the WT mice. Zingerone was selected for its enhancing activity on SIRT1 expression in THP-1 cells. Zingerone inhibited P. gingivalis-induced SIRT1 degradation and suppressed the P. gingivalis induced-IL-1β production. Moreover, zingerone increased LC3-II protein expression via SIRT1 pathway. In periodontitis mouse model, zingerone prevented the bone loss induced by P. gingivalis infecion.
Conclusions: SIRT-1 was involved in regulating host responses in P. gingivalis-induced inflammation. Zingerone showed anti-inflammatory effect by increasing autophagy through SIRT1 activation. Thus, zingerone acivated-SIRT1 plays an important role in controlling P. gingivalis-induced inflammation.
Methods: To induce inflammation, bone marrow-derived macrophages (BMDM) and THP-1 cells were infected with P. gingivalis. Protein expression and cytokine production were determined by Western blot and ELISA, respectively. C57BL/6 wild type (WT) and SIRT-1 transgenic mice were challenged with P. gingivalis for the induction of experimental periodontitis. Alveolar bone loss in each mouse was measured by Micro CT.
Results: P. gingivalis infection down-regulated SIRT1 expression and induced IL-1β production in BMDMs. IL-1β production and inflammasome activation were significantly reduced in BMDMs from SIRT-1 transgenic mice compared to the WT mice. Bone resorption was inhibited in SIRT1 transgenic mice compared to the WT mice. Zingerone was selected for its enhancing activity on SIRT1 expression in THP-1 cells. Zingerone inhibited P. gingivalis-induced SIRT1 degradation and suppressed the P. gingivalis induced-IL-1β production. Moreover, zingerone increased LC3-II protein expression via SIRT1 pathway. In periodontitis mouse model, zingerone prevented the bone loss induced by P. gingivalis infecion.
Conclusions: SIRT-1 was involved in regulating host responses in P. gingivalis-induced inflammation. Zingerone showed anti-inflammatory effect by increasing autophagy through SIRT1 activation. Thus, zingerone acivated-SIRT1 plays an important role in controlling P. gingivalis-induced inflammation.