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A Mouse Model for Pathogen-induced Chronic Inflammation at Local and Systemic Sites
Published on: August 8, 2014
PINK1-mediated mitophagy reduced inflammatory responses to Porphyromonas gingivalis in macrophages
Ke Jiang1,2, Jingwen Li1,2, Lishan Jiang1,2
1Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China.
Objective:
Mitochondria are strained by microbial stimuli in the periodontal niche. Damaged mitochondria are cleared by mitophagy. The purpose of the study was to explore whether mitophagy participated in the progress of periodontitis and whether activation of mitophagy can inhibit inflammatory responses to bacterial infection in macrophages.
Methods:
Mitophagy-related genes were measured in the healthy and inflamed human gingiva. Bone marrow-derived macrophages (BMDMs) were infected with Porphyromonas gingivalis. Dexmedetomidine, urolithin A, and resveratrol were used to activate mitophagy, while small interference RNA was utilized to knock down PTEN-induced putative protein kinase 1 (PINK1). Activation of mitophagy-related genes and colocalization of them were detected by Western blot and confocal imaging. Damages of mitochondria, accumulation of mitochondrial reactive oxygen species (mtROS), and production of IL-1β, IL-6, and TNF-α were measured.
Results:
Levels of mitophagy-related genes were decreased in inflamed periodontal tissues and P. gingivalis-infected BMDMs. Dexmedetomidine, urolithin A, and resveratrol activated mitophagy, leading to reduced mitochondria damages, decreased mtROS generation, and inhibited IL-1β, IL-6, and TNF-α production. PINK1 knockdown reduced dexmedetomidine, urolithin A, and resveratrol-induced anti-inflammatory effect.
Conclusion:
Inhibited mitophagy participated in the progress of periodontitis. Activation of mitophagy may become a therapeutic target during the progress of periodontitis by reducing mtROS.
Insights
Inhibited mitophagy contributes to periodontitis progression. Activating mitophagy, a cellular cleanup process, can reduce inflammation and mitochondrial damage, offering a potential therapeutic strategy for periodontitis.
Area of Science:
- Cellular Biology
- Immunology
- Periodontal Disease Research
Background:
- Mitochondria are crucial cellular components often damaged by microbial stimuli in the periodontal niche.
- Mitophagy, the selective degradation of damaged mitochondria, plays a role in maintaining cellular health.
- Periodontitis involves chronic inflammation driven by microbial infection, impacting periodontal tissues.
Purpose of the Study:
- To investigate the role of mitophagy in the pathogenesis of periodontitis.
- To determine if activating mitophagy can mitigate inflammatory responses in macrophages during bacterial infection.
Main Methods:
- Quantified mitophagy-related gene expression in healthy and inflamed human gingiva.
- Infected bone marrow-derived macrophages (BMDMs) with Porphyromonas gingivalis.
- Utilized dexmedetomidine, urolithin A, and resveratrol to activate mitophagy; employed small interference RNA to knockdown PINK1.
- Assessed mitophagy activation, mitochondrial damage, mitochondrial reactive oxygen species (mtROS), and pro-inflammatory cytokine production (IL-1β, IL-6, TNF-α).
Main Results:
- Decreased mitophagy-related gene levels were observed in inflamed periodontal tissues and P. gingivalis-infected BMDMs.
- Dexmedetomidine, urolithin A, and resveratrol treatments activated mitophagy, reducing mitochondrial damage and mtROS generation.
- These mitophagy-activating agents inhibited the production of IL-1β, IL-6, and TNF-α; PINK1 knockdown diminished these anti-inflammatory effects.
Conclusions:
- Impaired mitophagy is implicated in the progression of periodontitis.
- Targeting mitophagy activation presents a potential therapeutic strategy for periodontitis by reducing mitochondrial damage and inflammation.
