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MicroRNA-223 negatively regulates LPS-induced inflammatory responses by targeting NLRP3 in human dental pulp fibroblasts

Wang, Diya, Sun, Shukai, Xue, Ying, Qui, Jun, Ye, Tao, Zhang, Rong, Song, Bing, He, Wenxi, Zhang, Yaqing and Jiang, Wenkai 2021. MicroRNA-223 negatively regulates LPS-induced inflammatory responses by targeting NLRP3 in human dental pulp fibroblasts. International Endodontic Journal 54 (2) , pp. 241-254. 10.1111/iej.13413

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Abstract

Aim To investigate the effect of miR-223 on NLRP3, subsequently regulating the production of the NLRP3/CASP1 inflammasome pathway-mediated proinflammatory cytokines IL-1β and IL-18 in human dental pulp fibroblasts (HDPFs). Methodology Human dental pulp tissue (HDPT) and HDPFs were obtained from impacted third molars. The miR-223 mimics and inhibitor or NLRP3 plasmid were used to upregulate or downregulate miR-223 or NLRP3 in HDPFs, respectively. Computational prediction via TargetScan 5.1 and a luciferase reporter assay were conducted to confirm target association. The mRNA and protein expression of NLRP3, caspase-1, IL-1β and IL-18 were determined by qRT-PCR and western blotting, respectively. The release of IL-1β and IL-18 was analyzed by ELISA. The significance of the differences between the experimental and the control groups was determined by using one-way analysis of variance, P<0.05 indicated statistical significance. Results A decrease in miR-223 and an increase in NLRP3 in HDPT occurred during the transformation of reversible pulpitis into irreversible pulpitis compared to that in healthy pulp tissue (p<0.05). The computational prediction and luciferase reporter assay confirmed that NLRP3 was a direct target of miR-223 in HDPFs. The miR-223 inhibitor further promoted ATP plus LPS-induced NLRP3/CASP1 inflammasome pathway activation compared to the ATP plus LPS-induced group (p<0.05). In contrast, the miR-223 mimic significantly inhibited the NLRP3/CASP1 inflammasome pathway activation induced by ATP plus LPS compared to the ATP plus LPS-induced group (p<0.05). Conclusion MiR-223 serves as a negative regulator involved in the control of the production and secretion of proinflammatory cytokines mediated by the NLRP3/CASP1 inflammasome pathway by targeting NLRP3. These data provide insight into the potential regulatory effects of miRNAs on the NLRP3 inflammasome, thus opening up novel potential therapeutic avenues for future endodontic treatment.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Dentistry
Publisher: Wiley
ISSN: 0143-2885
Date of First Compliant Deposit: 15 September 2020
Date of Acceptance: 14 September 2020
Last Modified: 12 Oct 2021 06:32
URI: http://orca.cardiff.ac.uk/id/eprint/134868

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