Phospholipase C-γ1 (PLC-γ1), which interacts with a variety of signaling molecules through its two Src homology (SH) 2 domains and a single SH3 domain has been implicated in the regulation of many cellular functions. We demonstrate that PLC-γ1 acts as a guanine nucleotide exchange factor (GEF) of dynamin-1, a 100 kDa GTPase protein, which is involved in clathrin-mediated endocytosis of epidermal growth factor (EGF) receptor. Overexpression of PLC-γ1 increases endocytosis of the EGF receptor by increasing guanine nucleotide exchange activity of dynamin-1. The GEF activity of PLC-γ1 is mediated by the direct interaction of its SH3 domain with dynamin-1. EGF-dependent activation of ERK and serum response element (SRE) are both up-regulated in PC12 cells stably overexpressing PLC-γ1, but knockdown of PLC-γ1 by siRNA significantly reduces ERK activation. These results establish a new role for PLC-γ1 in the regulation of endocytosis and suggest that endocytosis of activated EGF receptors may mediate PLC-γ1-dependent proliferation.

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Background and Objectives Periodontal pathogens initiate various diseases and induce inflammatory host responses. The activation of inflammasomes triggers caspase‐1 and interleukin (IL)‐1β‐mediated pyroptosis via gasdermin D (GSDMD). Differentiated embryo chondrocyte 2 (Dec2) is a transcription repressor that controls the expression of genes involved in innate immune and inflammatory responses. However, the effects of Dec2 on inflammasome‐induced pyroptosis in periodontal tissues remain elusive. This study aimed to characterize the activation of Dec2 inflammasomes that contribute to P. gingivalis lipopolysaccharide (LPS)‐induced pyroptosis and its functional and regulatory importance in periodontal inflammation. Materials and Methods Human gingival fibroblasts (HGFs) and human periodontal ligament fibroblasts (HPDLFs) were stimulated with P. gingivalis LPS in vitro. An experimental periodontitis mouse model (wild‐type (WT) and Dec2KO) was established to profile periodontal pyroptosis. Results The results demonstrate that P. gingivalis LPS activates caspase‐1, caspase‐11, and NF‐κB in HGFs and in HPDLFs. siRNA knockdown of Dec2 stimulated the induction and further upregulated LPS‐induced pyroptosis in HGFs and HPDLFs, resulting in the release of IL‐1β. Further, a deficiency of Dec2 alleviated periodontal pyroptosis via the transcriptional induction of GSDMD. In addition, P. gingivalis‐induced IL‐1β expression and Dec2‐deficient mice subsequently increased the inflammatory effect of P. gingivalis in HGFs and in HPDLFs, confirming the importance of Dec2 in the activation of inflammasomes and the regulation of pyroptosis. Conclusion Our results demonstrate that Dec2 alleviates periodontal pyroptosis by regulating the expression of NF‐κB, caspase‐1 and GSDMD, suggesting that Dec2 is a crucial component of inflammasome activation and subsequent pyroptosis.

The number of missing teeth was associated with CCA IMT, and BOP% was associated with CCA IMT in females only. These associations were robust in never smokers. Our results suggest that tooth loss due to oral disease may play a role in subclinical carotid atherosclerosis.

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