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Enterococcus faecalis Lipoteichoic Acid-induced NLRP3 Inflammasome via the Activation of the Nuclear Factor Kappa B
Lina Wang1, Haiwei Jin2, Dandan Ye1
1Department of Endodontics and Periodontics, College of Stomatology, Dalian Medical University, Dalian, Liaoning Province, China.
Introduction:
We wished to examine the effects of the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome on periapical periodontitis induced by Enterococcus faecalis and to investigate the molecular mechanisms of lipoteichoic acid (LTA) derived from E. faecalis on the expression of the NLRP3 inflammasome.
Methods:
A model of periapical periodontitis by sealing E. faecalis into the pulp chambers of rats was established. We then examined the relationship between the expression, location, distribution, and concentration of NLRP3, caspase-1, and interleukin 1β with the inflammatory progression by immunohistochemistry and undertook correlation analyses. RAW264.7 cells were cultured in the absence or presence of LTA together with or without nuclear factor kappa B (NF-κB) inhibitor BAY 11-7082; NLRP3 inflammasome expression was measured by Western blotting, the enzyme-linked immunosorbent assay, and real-time quantitative polymerase chain reaction. An immunofluorescence study was conducted to further detect whether NF-κB can be completely inhibited by BAY 11-7082 or activated by LTA.
Results:
An animal model of periapical periodontitis was established successfully. Expression of NLRP3, caspase-1, and interleukin 1β protein was observed in the inflamed area. The expression of these 3 proteins had a significant positive correlation (P < .05). Overall, our results showed that, compared with the negative control group, LTA could directly activate expression of messenger RNA and protein of the NLRP3 inflammasome (P < .05), whereas BAY 11-7082 inhibited it (P < .05).
Conclusions:
Our results suggested that LTA can act as a directly stimulating factor associated with expression of the NLRP3 inflammasome during periapical periodontitis, which is mainly linked with the NF-κB signaling activation pathway.
Insights
Lipoteichoic acid (LTA) from Enterococcus faecalis activates the NLRP3 inflammasome in periapical periodontitis, primarily through NF-κB signaling. This study elucidates LTA's role in driving inflammation and provides therapeutic targets.
Area of Science:
- Oral biology
- Immunology
- Microbiology
Background:
- Periapical periodontitis is an inflammatory condition often caused by Enterococcus faecalis.
- The nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome plays a role in inflammatory diseases.
Purpose of the Study:
- To investigate the role of the NLRP3 inflammasome in Enterococcus faecalis-induced periapical periodontitis.
- To explore the molecular mechanisms by which lipoteichoic acid (LTA) from E. faecalis influences NLRP3 inflammasome expression.
Main Methods:
- Established a rat model of periapical periodontitis induced by E. faecalis.
- Utilized immunohistochemistry, Western blotting, ELISA, and qPCR to analyze NLRP3 inflammasome components (NLRP3, caspase-1, IL-1β).
- Investigated the involvement of the NF-κB signaling pathway using LTA and the NF-κB inhibitor BAY 11-7082 in RAW264.7 cells.
Main Results:
- NLRP3, caspase-1, and IL-1β expression correlated positively with inflammatory progression in the animal model.
- Lipoteichoic acid (LTA) directly activated NLRP3 inflammasome expression at both mRNA and protein levels.
- The NF-κB signaling pathway was identified as a key mediator in LTA-induced NLRP3 inflammasome activation.
Conclusions:
- Lipoteichoic acid (LTA) from Enterococcus faecalis directly stimulates NLRP3 inflammasome expression in periapical periodontitis.
- NF-κB signaling activation is the primary mechanism linking LTA to NLRP3 inflammasome expression.
- Targeting the LTA-NLRP3-NF-κB axis may offer therapeutic strategies for periapical periodontitis.
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