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Article Dans Une Revue International Endodontic Journal Année : 2023

Regulation of caries-induced pulp inflammation by NLRP3 inflammasome: A laboratory-based investigation

Banan Al Natour
  • Fonction : Auteur
Fionnuala Lundy
Yvonne Dombrowski
Ikhlas El Karim

Résumé

Abstract Aim To evaluate the expression and function of the nod‐like receptor pyrin domain containing 3 (NLRP3) inflammasome in caries induced pulpitis. Methodology NLRP3 expression was determined with immunohistochemistry in the dental pulp and qPCR in dental pulp cells (DPCs). THP‐1 macrophages expressing the apoptosis‐related speck‐like protein (ASC) and green fluorescent protein (GFP) fusion protein were used to assess NLRP3 inflammasome activation by live cell imaging, following treatment with lipopolysaccharide (LPS) and lipoteichoic acid (LTA). Caspase I inhibitor was used to confirm inflammasome activation. An ex‐vivo pulpitis model in which the DPCs were co‐cultured with THP‐1 macrophages was used to study the effect of the NLRP3 inflammasome inhibitor (MCC950), and cytokines were measured using ELISA and multiplex array. Data were analysed using the t‐test or anova followed by a Bonferroni post hoc test with the level of significance set at p ≤ .05. Results NLRP3 inflammasome was differentially expressed in dental pulp of sound and carious teeth. Treatment of DPCs with LTA significantly upregulates NLRP3 and IL‐1 β‐expression ( p < .05) and in induces more ASC specks formation compared to LPS. IL‐β release in response to LTA treatment is significantly reduced with Caspase I inhibitor suggesting inflammasome dependent mechanism ( p < .01). NLRP3‐specific inhibitor, MCC950, significantly reduced IL‐1β and IL‐6 in an ex‐vivo pulpitis model ( p < .01) but had no effect on IL‐8 or matrix metalloproteinase‐9 (MMP‐9). Conclusions Expression and upregulation of NLRP3 inflammasome with caries and LTA treatment suggest a role in caries‐induced pulpitis. NLRP3 inhibitor attenuated the release of selective inflammatory cytokines and could be a potential treatment target that merit further investigation.
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Dates et versions

hal-04490647 , version 1 (05-03-2024)

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Citer

Banan Al Natour, Fionnuala Lundy, Imad About, Charlotte Jeanneau, Yvonne Dombrowski, et al.. Regulation of caries-induced pulp inflammation by NLRP3 inflammasome: A laboratory-based investigation. International Endodontic Journal, 2023, 56 (2), pp.193-202. ⟨10.1111/iej.13855⟩. ⟨hal-04490647⟩
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