Exploring the involvement of NLRP3 and Il-1β in Osteoarthritis of the Hand: Results from a Pilot Study

Antonella Fioravanti, Sara Tenti, Megan McAllister, Melody El Chemaly, Amanda Eakin, Joseph McLaughlin, AJ Bjourson, Elena Frati, V. E. McGilligan, David Gibson, Sara Cheleschi

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Abstract

Hand osteoarthritis (HOA) includes different subsets; a particular and uncommon form is erosive HOA (EHOA). Interleukin (IL)-1β plays a crucial role in the pathogenesis of osteoarthritis (OA); it is synthesized as an inactive precursor which requires the intervention of a cytosolic multi-protein complexes, named inflammasomes for its activation.
The aim of this study was to investigate the involvement of IL-1β and the NLRP3 inflammasome in patients with EHOA and non-erosive HOA (NEHOA) compared to healthy controls. In particular, we evaluated the gene expression of IL-1β and NLRP3, the serum levels of IL-1β, IL-6, IL-17 and Tumor Necrosis Factor (TNF)-α and the protein levels of IL-1β and NLRP3. We also assessed the relationships between IL-1β and NLRP3 and clinical, laboratory and radiological findings.
Fifty-four patients with HOA (25 EHOA, 29 NEHOA) and 20 healthy subjects were included in the study. Peripheral blood mononuclear cells (PBMCs) gene and protein expression of IL-1β and NLRP3 was quantified by quantitative real-time PCR and western blot. IL-1β, IL-6, IL-17 and TNF-α serum levels were determined by ELISA.
IL-1β gene expression was significantly reduced (p=0.0208) in EHOA compared to healthy controls. NLRP3 protein levels were significantly increased in NEHOA group versus control (p=0.0063) and EHOA groups (p=0.0038). IL-1β serum levels weren’t significantly different across the groups; IL-6, IL-17 and TNF-α weren’t detectable in any sample. IL-1β concentrations were negatively correlated with Kellgren-Lawrence score in the whole population (r= -0.446; p=0.0008) and in NEHOA (r= -0.608; p=0.004), while IL-1β gene expression was positively correlated with the number of joint swellings in EHOA group (r=0.512; p=0.011).
Taken together, our results, showing poorly detectable IL-1β concentrations and minimal inflammasome activity in the PBMCs of HOA patients, suggest a low grade of systemic inflammation in HOA. This evidence does not preclude a possible involvement of these factors at local level.
Original languageEnglish
Article number2363460
Number of pages13
JournalMediators of Inflammation
Volume2019
DOIs
Publication statusPublished (in print/issue) - 10 Mar 2019

Bibliographical note

Funding Information:
This work was funded by a grant awarded to AJB to establish the Northern Ireland Centre for Stratified Medicine, funded under the European Union Regional Development Fund (ERDF) EU Sustainable Competitiveness Programme for Northern Ireland and the Northern Ireland Public Health Agency (HSC R&D). A.J.B. and D.S.G. wish to acknowledge the award of Ph.D. fellowships from Department for Employment, Northern Ireland, UK.

Publisher Copyright:
© 2019 Antonella Fioravanti et al.

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