期刊
JOURNAL OF ORAL MICROBIOLOGY
卷 14, 期 1, 页码 -出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/20002297.2021.2015130
关键词
MARK4; NLRP3 inflammasome; pyroptosis; periodontitis; Porphyromonas gingivalis
类别
资金
- National Natural Science Foundation of China [81670996]
- Nanjing Medical Science and Technique Development Foundation [QRX17025, QRX17081]
- Nanjing Clinical Research Center for Oral Diseases [2019060009]
This study found that MARK4 promotes the activation of NLRP3 inflammasome and pyroptosis in P. gingivalis-infected macrophages by affecting microtubule dynamics. Inhibition of MARK4 may be a potential therapeutic target for regulating NLRP3 inflammasome during the progress of periodontitis.
Background Microtubule dynamics plays a crucial role in the spatial arrangement of cell organelles and activation of the NLRP3 inflammasome. Purpose This study aimed to explore whether microtubule affinity regulating kinase 4 (MARK4) can be a therapeutic target of periodontitis by affecting microtubule dynamics and NLRP3 inflammasome-mediated pyroptosis in macrophages. Materials and Methods The NLRP3 inflammasome-related genes and MARK4 were measured in the healthy and inflamed human gingival tissues. Bone marrow-derived macrophages (BMDMs) were infected with Porphyromonas gingivalis, while the MARK4 inhibitors (OTSSP167 and Compound 50) and small interference RNA were utilized to restrain MARK4. Apoptosis-associated speck-like protein (ASC) speck was detected by confocal, and levels of interleukin-1 beta (IL-1 beta), as well as IL-18, were assessed by ELISA. Results Increased staining and transcription of MARK4, NLRP3, ASC, and Caspase-1 were observed in the inflamed gingiva. P. gingivalis infection promoted MARK4 expression and the NLRP3 inflammasome in BMDMs. Inhibition of MARK4 decreased LDH release, IL-1 beta and IL-18 production, ASC speck formation, and the pyroptosis-related genes transcription. Furthermore, MARK4 inhibition reduced microtubule polymerization and acetylation in P. gingivalis-infected BMDMs. Conclusions MARK4 promoted NLRP3 inflammasome activation and pyroptosis in P. gingivalis-infected BMDMs by affecting microtubule dynamics. MARK4 inhibition might be a potential target in regulating the NLRP3 inflammasome during periodontitis progress.
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