International dental journal · 2025
Lipoteichoic Acid Stimulation of Macrophages Causes Mitochondrial Dysfunction.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
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История · было → стало
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Liu Siyao, Liu Xin, Li Guixin, Liu Huan, Zhang Weiwei, Pan Shuang
Аннотация
OBJECTIVES: This study aimed to investigate the role of mitochondrial dysfunction in the pathogenesis of Enterococcus faecalis and its lipoteichoic acid (LTA)-induced refractory apical periodontitis, and then to evaluate whether the modulation of mitochondrial dynamics with Mdivi-1 could alleviate the ensuing inflammatory response..
METHODS: An LTA-induced macrophage model was established to simulate the inflammatory environment of apical periodontitis. Changes in inflammatory factors, mitochondrial morphology, dynamics-related proteins, autophagy markers, and reactive oxygen species (ROS) were analysed. The mitochondrial division inhibitor Mdivi-1 was applied to assess its effects on mitochondrial and inflammatory parameters.
RESULTS: In the in vivo model, E. faecalis infection successfully induced apical periodontitis, as confirmed by radiographic evidence of periapical bone loss and histological observation of inflammatory cell infiltration. These lesions exhibited a significant upregulation of the pro-inflammatory marker iNOS, concurrently with a downregulation of the mitochondrial protein MFN-2. Consistent with the in vivo findings, LTA stimulation in a cellular model significantly increased the expression of inflammatory mediators (NLRC4, iNOS, NF-κB, Caspase-1) and induced mitochondrial dysfunction, characterised by morphological disruption, dysregulated dynamics, impaired autophagy and elevated ROS levels. Critically, Mdivi-1 treatment mitigated these abnormalities by improving mitochondrial structure and function, normalising dynamics-related protein expression and consequently reducing the inflammatory response.
CONCLUSIONS: Mitochondrial dysfunction plays a central role in LTA-driven inflammatory processes in apical periodontitis. Targeting mitochondrial dynamics with Mdivi-1 can restore mitochondrial function and mitigate macrophage-mediated inflammation, revealing a key mechanism underlying refractory apical periodontitis.
CLINICAL SIGNIFICANCE: This study suggests that enhancing mitochondrial function with agents such as Mdivi-1 could serve as a novel therapeutic strategy for refractory apical periodontitis by modulating immune responses and reducing chronic inflammation, potentially improving treatment outcomes in clinically challenging cases.
METHODS: An LTA-induced macrophage model was established to simulate the inflammatory environment of apical periodontitis. Changes in inflammatory factors, mitochondrial morphology, dynamics-related proteins, autophagy markers, and reactive oxygen species (ROS) were analysed. The mitochondrial division inhibitor Mdivi-1 was applied to assess its effects on mitochondrial and inflammatory parameters.
RESULTS: In the in vivo model, E. faecalis infection successfully induced apical periodontitis, as confirmed by radiographic evidence of periapical bone loss and histological observation of inflammatory cell infiltration. These lesions exhibited a significant upregulation of the pro-inflammatory marker iNOS, concurrently with a downregulation of the mitochondrial protein MFN-2. Consistent with the in vivo findings, LTA stimulation in a cellular model significantly increased the expression of inflammatory mediators (NLRC4, iNOS, NF-κB, Caspase-1) and induced mitochondrial dysfunction, characterised by morphological disruption, dysregulated dynamics, impaired autophagy and elevated ROS levels. Critically, Mdivi-1 treatment mitigated these abnormalities by improving mitochondrial structure and function, normalising dynamics-related protein expression and consequently reducing the inflammatory response.
CONCLUSIONS: Mitochondrial dysfunction plays a central role in LTA-driven inflammatory processes in apical periodontitis. Targeting mitochondrial dynamics with Mdivi-1 can restore mitochondrial function and mitigate macrophage-mediated inflammation, revealing a key mechanism underlying refractory apical periodontitis.
CLINICAL SIGNIFICANCE: This study suggests that enhancing mitochondrial function with agents such as Mdivi-1 could serve as a novel therapeutic strategy for refractory apical periodontitis by modulating immune responses and reducing chronic inflammation, potentially improving treatment outcomes in clinically challenging cases.