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Lookup NU author(s): Shannon JamiesonORCiD, Dr Philip Hyde, Patrick Card, Professor David Deehan, Josh Kirby, Professor Alison Tyson-Capper
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Copyright © 2025 Jamieson, Hyde, Card, Deehan, Kirby and Tyson-Capper.Objectives: The aim of this study was to assess potential pro-inflammatory responses induced in a human monocyte cell line by poly-ether-ether-ketone (PEEK) particles. Investigations also focussed on the role of toll-like receptor 4 (TLR4) and reactive oxygen species (ROS) in immune responses to PEEK. Methods: PEEK particles were generated using a four-station multi-directional pin-on-plate wear simulator and used to treat THP-1 macrophages for 24 h at dosages of 0.5–50 μm3 per cell. THP-1 cell supernatant was used for protein secretion analysis using ELISA and gene expression investigations using RT-qPCR. TLR4 inhibition was also achieved using CLI-095 by treating cells prior to PEEK exposure. ROS production was investigated following PEEK treatment. IL-1β secretion was investigated by treating PEEK-exposed cells to 5 mM ATP for 1 h in order to assess the role of the inflammasome. Results: PEEK particles were not immediately cytotoxic to THP-1 macrophages and induced a significant increase in gene expression and protein secretion of IL-8, CCL2, CCL3, and CCL4 at the highest dose (p < 0.0001). This increase in pro-inflammatory genes and proteins was not inhibited following blockade of TLR4. ROS production was significantly upregulated in the PEEK-treated cells and IL-1β secretion was also significantly increased following the addition of ATP to PEEK-exposed THP-1 cells. Conclusion: PEEK particles are capable of inducing a pro-inflammatory phenotype in a human macrophage cell line which is not a result of TLR4 activation. PEEK particles do act in a PAMP-like manner and are able to induce ROS production as well as initiate inflammasome activation.
Author(s): Jamieson S, Hyde P, Card P, Deehan D, Kirby J, Tyson-Capper A
Publication type: Article
Publication status: Published
Journal: Frontiers in Bioengineering and Biotechnology
Year: 2025
Volume: 13
Online publication date: 05/08/2025
Acceptance date: 25/07/2025
Date deposited: 01/09/2025
ISSN (electronic): 2296-4185
Publisher: Frontiers Media SA
URL: https://doi.org/10.3389/fbioe.2025.1507248
DOI: 10.3389/fbioe.2025.1507248
Data Access Statement: The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation
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