Neutrophil extracellular traps induced by diabetes aggravate periodontitis by inhibiting janus kinase/signal transducers and activators of transcription signaling in macrophages

Diabetes, which is a systemic disease, increases susceptibility to destructive periodontal diseases, which are characterized by infectious susceptibility, but the potential mechanisms remain unknown. The aim of this study was to investigate the mechanism of high glucose environment promoting the occ...

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Bibliographic Details
Published in:Journal of dental sciences 2024-09
Main Authors: Wen, Jing, Li, Jingru, Wu, Zhenhuan
Format: Article
Language:English
Subjects:
Diabetic periodontitis
JAK-STAT pathway
Macrophage polarization
Neutrophil extracellular trap
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Summary:Diabetes, which is a systemic disease, increases susceptibility to destructive periodontal diseases, which are characterized by infectious susceptibility, but the potential mechanisms remain unknown. The aim of this study was to investigate the mechanism of high glucose environment promoting the occurrence and development of local periodontal inflammation. In this study, the effects of neutrophil extracellular traps (NETs) on macrophage polarization and the mechanism were designed to verify whether this course plays a role in periodontal tissue impairment associated with diabetes. Here, we examined the impact of NETs on macrophages in vitro. NETs were isolated from cultures of neutrophils exposed to hyperglycemia. Mouse models of diabetic periodontitis (DP) and macrophage polarization were developed, and the degrees of NET formation in the periodontal tissue of DP mice were assessed. Furthermore, western blotting was performed to analyze the related mechanisms. The results revealed that hyperglycemia induced the formation of NETs, and abundant NET formation led to proinflammatory cytokine secretion by macrophages and low expression of JAK-2 and STAT-3 in vitro and in vivo. NETs regulated macrophage polarization through the JAK/STAT pathway. These results suggest that NETs target proinflammatory cytokine secretion via the JAK/STAT pathway and may play important roles in DP progression and macrophage polarization, which indicates that therapeutically referring to this regulatory pathway might be a promising method for treating diabetes-associated inflammatory diseases.
ISSN:1991-7902
DOI:10.1016/j.jds.2024.09.006