The effects of NLRP3 inflammasome inhibition or knockout in experimental apical periodontitis induced in mice.

Autor: Pucinelli CM; Department of Pediatric Dentistry (DCI), School of Dentistry of Ribeirão Preto, University of São Paulo (FORP/USP), Avenida do Café, s/n, Vila Monte Alegre, Ribeirão Preto, São Paulo, Brazil., da Silva RAB; Department of Pediatric Dentistry (DCI), School of Dentistry of Ribeirão Preto, University of São Paulo (FORP/USP), Avenida do Café, s/n, Vila Monte Alegre, Ribeirão Preto, São Paulo, Brazil.; Graduate Program in Pediatric Dentistry, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil., Nelson-Filho P; Department of Pediatric Dentistry (DCI), School of Dentistry of Ribeirão Preto, University of São Paulo (FORP/USP), Avenida do Café, s/n, Vila Monte Alegre, Ribeirão Preto, São Paulo, Brazil.; Graduate Program in Pediatric Dentistry, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil., Lima RB; Department of Pediatric Dentistry (DCI), School of Dentistry of Ribeirão Preto, University of São Paulo (FORP/USP), Avenida do Café, s/n, Vila Monte Alegre, Ribeirão Preto, São Paulo, Brazil. ricardobarbosalima@usp.br.; Graduate Program in Pediatric Dentistry, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil. ricardobarbosalima@usp.br., Lucisano MP; Department of Pediatric Dentistry (DCI), School of Dentistry of Ribeirão Preto, University of São Paulo (FORP/USP), Avenida do Café, s/n, Vila Monte Alegre, Ribeirão Preto, São Paulo, Brazil.; Graduate Program in Pediatric Dentistry, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil., Marchesan JT; Department of Periodontology, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., da Silva LAB; Department of Pediatric Dentistry (DCI), School of Dentistry of Ribeirão Preto, University of São Paulo (FORP/USP), Avenida do Café, s/n, Vila Monte Alegre, Ribeirão Preto, São Paulo, Brazil.; Graduate Program in Pediatric Dentistry, School of Dentistry of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.
Jazyk: angličtina
Zdroj: Clinical oral investigations [Clin Oral Investig] 2024 Apr 30; Vol. 28 (5), pp. 285. Date of Electronic Publication: 2024 Apr 30.
DOI: 10.1007/s00784-024-05691-6
Abstrakt: Objective: To evaluate the effects of NLRP3 inflammasome inhibition or knockout in experimental apical periodontitis (AP) induced in mice.
Methods: The experimental AP was induced by pulpal exposure. To evaluate NLRP3-specific inhibitor medication (MCC950), WT mice received intraperitoneal injections, while the control received PBS (n = 10). In addition, to evaluate NLRP3 knockout, 35 wild-type (WT) and 35 NLRP3 -/- mice were divided into a control group (without pulpal exposure, n = 5) and three experimental groups: after 2, 14 and 42 days after pulpal exposure (n = 10). Microscopic and molecular analyzes were carried out using a significance level of 5%.
Results: Exposure to MCC950 did not affect the periapical lesion size after 14 days (P = 0.584). However, exposed mice had a lower expression of IL-1β, IL-18 and caspase-1 (P = 0.010, 0.016 and 0.002, respectively). Moreover, NLRP3 -/- mice showed a smaller periapical lesion after 14 and 42 days (P = 0.023 and 0.031, respectively), as well as a lower expression of IL-1β after 42 days (P < 0.001), of IL-18 and caspase-1 after 14 (P < 0.001 and 0.035, respectively) and 42 days (P = 0.002 and 0.002, respectively). NLRP3 -/- mice also showed a lower mRNA for Il-1β, Il-18 and Casp1 after 2 (P = 0.002, 0.036 and 0.001, respectively) and 14 days (P = 0.002, 0.002 and 0.001, respectively).
Conclusions: NLRP3 inflammasome inhibition or knockout can attenuate the inflammatory events that result in the periapical lesion (AP) formation after pulpal exposure in mice.
Clinical Relevance: The NLRP3 inflammasome may be a therapeutic target for AP, and new approaches may verify the impact of its inhibition (through intracanal medications or filling materials) on the bone repair process and treatment success.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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