Regulation of caries‐induced pulp inflammation by NLRP3 inflammasome: a laboratory‐based investigation

Banan Al Natour, Fionnuala T. Lundy, Imad About, Charlotte Jeanneau, Yvonne Dombrowski, Ikhlas A. El Karim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)
112 Downloads (Pure)

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.


Original languageEnglish
Pages (from-to)193-202
Number of pages10
JournalInternational Endodontic Journal
Volume56
Issue number2
Early online date12 Nov 2022
DOIs
Publication statusPublished - Feb 2023

Bibliographical note

Output related to pulpitis treatment project
Role: Senior/corresponding author
Journal ranking 7/92 in dentistry; IF 5.1, SNIP 1.6

Keywords

  • ORIGINAL ARTICLE
  • ORIGINAL ARTICLES
  • caries bacteria
  • cell death
  • NLRP3 inflammasome
  • pulp death
  • pulpitis
  • vital pulp treatment

ASJC Scopus subject areas

  • General Dentistry

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