Inhibition of Dec1 provides biological insights into periodontal pyroptosis. Issue 1 (1st January 2021)

• Record Type: Journal Article
• Authors: Oka, Shunichi; Li, Xiaoyan; Zhang, Fengzhu; Tewari, Nitesh; Wang, Chen; Kim, Il-Shin; Zhong, Liangjun; Hamada, Nobushiro; Oi, Yoshiyuki; Makishima, Makoto; Liu, Yi; Bhawal, Ujjal K.
• Is Part Of: All life. Volume 14:Issue 1(2021)
• Page Start: 300
• Page End: 307
• Publication Date: 2021-01-01
• Subjects: Dec1 -- pyroptosis -- cleaved-caspase-1 -- cleaved-GSDMD -- periodontal inflammation -- knock-out animal model; Life sciences -- Periodicals; Biology -- Periodicals; Electronic journals; Periodicals; 570.5
• DOI: 10.1080/26895293.2021.1915886
• Languages: English
• ISSNs: 2689-5293

Abstract

Abstract : Intracellular signaling complexes of the innate immune system orchestrate the development of inflammation . Porphyromonas gingivalis is a commensal bacterium that induces periodontal pyroptosis. The transcription factor Dec1 can regulate the expression of inflammatory molecules. In this study, we investigated whether a deficiency of Dec1 activates/represses Caspase-1 and/or Gasdermin-D in periodontal pyroptosis, resulting in the release of the proinflammatory mediator interleukin-1β. Dec1 expression in human periodontal ligament fibroblasts (HPDLFs) treated with P. gingivalis lipopolysaccharide (LPS) was assessed and pyroptosis activation was determined by microscopy, qRT-PCR and Western blot analysis. Moreover, a siRNA targeting Dec1 was introduced into HPDLFs to determine the function of Dec1 in periodontal pyroptosis and a Dec1-deficient experimental mouse model of periodontitis was used. Treatment of HPDLFs with P. gingivalis LPS-stimulated levels of cleaved-Caspase-1 and cleaved-GSDMD and increased levels of phosphorylated NF-κB and interleukin-1β. In contrast, Dec1 knockdown maintained cellular homeostasis with low levels of pyroptosis. Treatment with P. gingivalis alleviated periodontal pyroptosis in PDLFs of wild-type mice and a Dec1 deficiency subsequently repressed the inflammatory effect of P. gingivalis . These results reveal for the first time the novel function of Dec1 in periodontal pyroptosis, suggesting that Dec1 is a crucial target to prevent periodontal inflammation.