Enterococcus faecalis Lipoteichoic Acid-induced NLRP3 Inflammasome via the Activation of the Nuclear Factor Kappa B Pathway.
BACKGROUND
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.
Department of Endodontics and Periodontics, College of Stomatology, Dalian Medical University, Dalian, Liaoning Province, China.
Lina
L
Wang
Department of Oral Basic Science, College of Stomatology, Dalian Medical University, Dalian, Liaoning Province, China.
Haiwei
H
Jin
Department of Endodontics and Periodontics, College of Stomatology, Dalian Medical University, Dalian, Liaoning Province, China.
Dandan
D
Ye
Department of Endodontics and Periodontics, College of Stomatology, Dalian Medical University, Dalian, Liaoning Province, China.
Jiaojiao
J
Wang
Department of Endodontics and Periodontics, College of Stomatology, Dalian Medical University, Dalian, Liaoning Province, China.
Xiang
X
Ao
Department of Endodontics and Periodontics, College of Stomatology, Dalian Medical University, Dalian, Liaoning Province, China.
Ming
M
Dong
Department of Endodontics and Periodontics, College of Stomatology, Dalian Medical University, Dalian, Liaoning Province, China. Electronic address: 13840886663@139.com.
Weidong
W
Niu
D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D013293:Enterococcus faecalis; D007150:Immunohistochemistry; D058847:Inflammasomes / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism*; D010485:Periapical Periodontitis / Q000382:microbiology*; D010586:Phagocytes; D051381:Rats; D017207:Rats, Sprague-Dawley; D013682:Teichoic Acids / Q000494:pharmacology*
D058847:Inflammasomes; D008070:Lipopolysaccharides; D016328:NF-kappa B; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C573346:Nlrp3 protein, rat; D013682:Teichoic Acids; C009900:lipoteichoic acid
Enterococcus faecalis; NLRP3 inflammasome, periapical periodontitis; lipoteichoic acid