2. Academic Validation
  3. Hyperglycemia Aggravates Periodontitis via Autophagy Impairment and ROS-Inflammasome-Mediated Macrophage Pyroptosis

Hyperglycemia Aggravates Periodontitis via Autophagy Impairment and ROS-Inflammasome-Mediated Macrophage Pyroptosis

  • Int J Mol Sci. 2023 Mar 27;24(7):6309. doi: 10.3390/ijms24076309.
Zhenxing Zhao 1 2 3,  Ye Ming 1 2 3,  Xiang Li 1 2 3,  Hao Tan 1 2 3,  Xinyi He 1 2 3,  Lan Yang 1 2 3,  Jinlin Song 1 2 3,  Leilei Zheng 1 2 3
Affiliations

Affiliations

  • 1 College of Stomatology, Chongqing Medical University, Chongqing 401147, China.
  • 2 Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing 401147, China.
  • 3 Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing 401147, China.
PMID: 37047282 DOI: 10.3390/ijms24076309
Abstract

Macrophage Pyroptosis drives the secretion of IL-1β, which has been recently reported to be a featured salivary biomarker for discriminating periodontitis in the presence of diabetes. This study aimed to explore whether macrophage Pyroptosis plays a role in the development of diabetes mellitus-periodontitis, as well as potential therapeutic strategies. By establishing a model of experimental diabetes mellitus-periodontitis in rats, we found that IL-1β and gasdermin D were highly expressed, leading to aggravated destruction of periodontal tissue. MCC950, a potent and selective molecule inhibitor of the NLRP3 inflammasome, effectively inhibited macrophage Pyroptosis and attenuated alveolar bone losses in diabetes mellitus-periodontitis. Consistently, in vitro, high glucose could induce macrophage Pyroptosis and thus promoted IL-1β production in macrophages stimulated by lipopolysaccharide. In addition, Autophagy blockade by high glucose via the mTOR-ULK1 pathway led to severe oxidative stress response in macrophages stimulated by lipopolysaccharide. Activation of Autophagy by rapamycin, clearance of mitochondrial ROS by mitoTEMPO, and inhibition of inflammasome by MCC950 could significantly reduce macrophage Pyroptosis and IL-1β secretion. Our study demonstrates that hyperglycemia promotes IL-1β production and Pyroptosis in macrophages suffered by periodontal microbial stimuli. Modulation of Autophagy activity and specific targeting of the ROS-inflammasome pathway may offer promising therapeutic strategies to alleviate diabetes mellitus-periodontitis.

Keywords

MCC950; autophagy; hyperglycemia; oxidative stress; periodontal disease; pyroptosis.

Figures
Products