Porphyromonas gingivalis induces an inflammatory response via the cGAS-STING signaling pathway in a periodontitis mouse model

Periodontitis is an inflammatory disease initiated by periodontopathogenic bacteria in the dental plaque biofilms. Understanding the role of Porphyromonas gingivalis (P. gingivalis), a keystone pathogen associated with chronic periodontitis, in the inflammatory response is crucial. Herein, we investigated whether P. gingivalis infection triggers the expression of the type I IFN gene and various cytokines and leads to activation of the cGAMP synthase-stimulator of IFN genes (cGAS-STING) pathway both in vitro and in a mouse model. Additionally, in an experimental model of periodontitis using P. gingivalis, StingGt mice showed lower levels of inflammatory cytokines and bone resorption than wild-type mice. Furthermore, we report that a STING inhibitor (SN-011) significantly decreased inflammatory cytokine production and osteoclast formation in a periodontitis mouse model with P. gingivalis. In addition, STING agonist (SR-717) -treated periodontitis mice displayed enhanced macrophage infiltration and M1 macrophage polarization in periodontal lesions compared with that in vehicle-treated periodontitis mice. In conclusion, our results demonstrate that the cGAS-STING signaling pathway may be one of the key mechanisms crucial for the P. gingivalis-induced inflammatory response that leads to chronic periodontitis.

 

Comments:

This study dives deep into the role of Porphyromonas gingivalis in causing periodontitis and investigates the specific mechanisms triggering the inflammatory response. The focus is on the cGAS-STING signaling pathway, examining how P. gingivalis infection affects gene expression, cytokine production, and bone resorption both in vitro and in a mouse model.

The findings indicate that the cGAS-STING pathway plays a significant role in the inflammatory response triggered by P. gingivalis. StingGt mice, lacking the STING gene, displayed lower levels of inflammatory cytokines and reduced bone resorption compared to wild-type mice when exposed to P. gingivalis. Moreover, the study reports that inhibiting STING using SN-011 decreased inflammatory cytokine production and osteoclast formation in a mouse model of periodontitis caused by P. gingivalis.

Conversely, stimulating the STING pathway with SR-717 in the same periodontitis model intensified macrophage infiltration and polarization toward M1 macrophages in the periodontal lesions.

Overall, the research suggests that the cGAS-STING signaling pathway is a crucial mechanism involved in the inflammatory response triggered by P. gingivalis, contributing to the development of chronic periodontitis. Manipulating this pathway, either through inhibition or stimulation, affected the severity of inflammation, cytokine production, and bone resorption in the experimental models studied.

Related Products

Cat.No.	Product Name	Information
E1066	SN-011	SN-011 is a STING-specific antagonist with IC50 of 76 nM.

Related Targets

STING