Zingerone-Induced Autophagy Suppresses IL-1 beta Production by Increasing the Intracellular Killing of Aggregatibacter actinomycetemcomitans in THP-1 Macrophages

Periodontitis is caused by the inflammation of tooth-supporting tissue by pathogens such as Aggregatibacter actinomycetemcomitans. Interleukin-1 beta (IL-1 beta), a pro-inflammatory cytokine, triggers a series of inflammatory reactions and promotes bone resorption. The aim of this study was to examine the molecular mechanism and anti-inflammatory function of zingerone, a dietary phenolic found in Zingiber officinale, on periodontal inflammation induced by A. actinomycetemcomitans. Zingerone attenuated A. actinomycetemcomitans-induced nitric oxide (NO) production by inhibiting the expression of inducible nitric oxide synthase (iNOS) in THP-1 macrophages. Zingerone also inhibited the expression of tumor necrosis factor (TNF)- alpha, IL-1 beta, and their signal pathway molecules including the toll-like receptor (TLR)/mitogen-activated protein kinase (MAPKase). In particular, zingerone suppressed the expression of absent in melanoma 2 (AIM2) inflammasome components on IL-1 beta production. Moreover, zingerone enhanced autophagosome formation and the expressions of autophagy-associated molecules. Interestingly, zingerone reduced the intracellular survival of A. actinomycetemcomitans. This was blocked by an autophagy inhibitor, which reversed the decrease in IL-1 beta production by zingerone. Finally, zingerone alleviated alveolar bone absorption in an A. actnomycetemcomitans-induced periodontitis mice model. Our data suggested that zingerone has potential use as a treatment for periodontal inflammation induced by A. actinomycetemcomitans.