ETC-1002 Attenuates Lipopolysaccharide-Induced Inflammation in RAW264.7 Cells the AMPK/NF-B Pathway and Exerts Ameliorative Effects in Experimental Periodontitis in Mice.

BACKGROUND

Clinically, the failure of periodontal therapy stems largely from an inability to control the inflammatory response. Resolution of inflammation is an active, energy-requiring repair process, not merely a passive termination of inflammation. AMP-activated protein kinase (AMPK), a key energy sensor, has been shown to negatively regulate inflammatory signaling pathways. Thus, there is a crucial need for new therapeutic strategies to modulate AMPK and to promote enhanced resolution of inflammation. This study is aimed at investigating the anti-inflammatory effects of ETC-1002 through modulating AMPK in periodontitis.

METHODS

RAW264.7 cells were infected with -LPS in the presence or absence of ETC-1002, following which the expression levels of proinflammatory cytokines and inflammation signaling-related proteins were evaluated by real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. ETC-1002 was applied in a murine model of periodontitis to determine its anti-inflammatory effect . Histological changes were investigated by hematoxylin and eosin (H&E) staining, the levels of proinflammatory cytokines were detected using immunohistochemistry, and alveolar bone height was measured using micro-CT imaging.

RESULTS

ETC-1002 inhibited the production of proinflammatory cytokines, promoted AMPK phosphorylation, and decreased IB and NF-B p65 phosphorylation levels in -LPS-treated RAW264.7 macrophages. The inhibitory effects of ETC-1002 on the production of proinflammatory mediators were significantly abrogated by siRNA-mediated silencing of AMPK in RAW264.7 cells. , ETC-1002 inhibited inflammatory cell infiltration, the expression of proinflammatory cytokines, and the inflammation-mediated destruction of alveolar bone in mice with experimental periodontitis. The anti-inflammatory effect of ETC-1002 in the periodontium could be reversed by the administration of Compound C, an AMPK inhibitor.

CONCLUSIONS

ETC-1002 exerts anti-inflammatory effects in -LPS-treated RAW264.7 cells the AMPK/NF-B pathway and inhibits the progress of experimental periodontitis in mice in an AMPK signaling-dependent manner . These results provide evidence for the beneficial effects of ETC-1002 in the treatment of periodontitis.