Journal of Periodontal and Implant Science

Korean Academy of Periodontology (대한치주과학회)
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Dec2 inhibits macrophage pyroptosis to promote periodontal homeostasis

  • He, Dawei (Department of Periodontics and Oral Mucosa Disease, Dalian Stomatological Hospital) ;
  • Li, Xiaoyan (Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology) ;
  • Zhang, Fengzhu (Shenyang Medical College School of Stomatology) ;
  • Wang, Chen (Department of Histology, Nihon University School of Dentistry at Matsudo) ;
  • Liu, Yi (Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology) ;
  • Bhawal, Ujjal K. (Department of Oral Health, Kanagawa Dental University) ;
  • Sun, Jiang (Department of Periodontics and Oral Mucosa Disease, Dalian Stomatological Hospital)
  • Received : 2021.02.21
  • Accepted : 2021.07.27
  • Published : 2022.02.28
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Abstract

Purpose: Macrophages play crucial roles as early responders to bacterial pathogens and promote/ or impede chronic inflammation in various tissues. Periodontal macrophage-induced pyroptosis results in physiological and pathological inflammatory responses. The transcription factor Dec2 is involved in regulating immune function and inflammatory processes. To characterize the potential unknown role of Dec2 in the innate immune system, we sought to elucidate the mechanism that may alleviate macrophage pyroptosis in periodontal inflammation. Methods: Porphyromonas gingivalis lipopolysaccharide (LPS) was used to induce pyroptosis in RAW 264.7 macrophages. Subsequently, we established an LPS-stimulated Dec2 overexpression cellular model in macrophages. Human chronic periodontitis tissues were employed to evaluate potential changes in inflammatory marker expression and pyroptosis. Finally, the effects of Dec2 deficiency on inflammation and pyroptosis were characterized in a P. gingivalis-treated experimental periodontitis Dec2-knockout mouse model. Results: Macrophages treated with LPS revealed significantly increased messenger RNA expression levels of Dec2 and interleukin (IL)-1β. Dec2 overexpression reduced IL-1β expression in macrophages treated with LPS. Overexpression of Dec2 also repressed the cleavage of gasdermin D (GSDMD), and the expression of caspase-11 was concurrently reduced in macrophages treated with LPS. Human chronic periodontitis tissues showed significantly higher gingival inflammation and pyroptosis-related protein expression than non-periodontitis tissues. In vivo, P. gingivalis-challenged mice exhibited a significant augmentation of F4/80, tumor necrosis factor-α, and IL-1β. Dec2 deficiency markedly induced GSDMD expression in the periodontal ligament of P. gingivalis-challenged mice. Conclusions: Our findings indicate that Dec2 deficiency exacerbated P. gingivalis LPS-induced periodontal inflammation and GSDMD-mediated pyroptosis. Collectively, our results present novel insights into the molecular functions of macrophage pyroptosis and document an unforeseen role of Dec2 in pyroptosis.

Keywords

Acknowledgement

We would like to thank Professor Y. Kato for providing Dec2KO mice; Professor N. Hamada, Dr. T. Toyama, and Dr. T. Sato for the P. gingivalis treatment; and the staff of the animal facility for care of the mice. We thank Dr. Y. Fujita for technical assistance.

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