Exploring the involvement of NLRP3 and Il-1β in osteoarthritis of the hand: results from a pilot study

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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.
LanguageEnglish
Number of pages13
JournalMediators of Inflammation
Publication statusAccepted/In press - 19 Dec 2018

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Interleukin-1beta
Osteoarthritis
Hand
Inflammasomes
Interleukin-17
Gene Expression
Interleukin-6
Tumor Necrosis Factor-alpha
Blood Cells
Serum
Proteins
4-hexyloxyaniline
Real-Time Polymerase Chain Reaction
Healthy Volunteers
Joints
Western Blotting
Enzyme-Linked Immunosorbent Assay
Inflammation

Cite this

@article{167447d1f5ab4644b4eb04f8bc01a6d0,
title = "Exploring the involvement of NLRP3 and Il-1β in osteoarthritis of the hand: results from a pilot study",
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.",
author = "David Gibson and McGilligan, {V. E.} and AJ Bjourson and {El Chemaly}, Melody and Joseph McLaughlin",
year = "2018",
month = "12",
day = "19",
language = "English",
journal = "Mediators of Inflammation",
issn = "1466-1861",

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TY - JOUR

T1 - Exploring the involvement of NLRP3 and Il-1β in osteoarthritis of the hand: results from a pilot study

AU - Gibson, David

AU - McGilligan, V. E.

AU - Bjourson, AJ

AU - El Chemaly, Melody

AU - McLaughlin, Joseph

PY - 2018/12/19

Y1 - 2018/12/19

N2 - 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.

AB - 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.

M3 - Article

JO - Mediators of Inflammation

T2 - Mediators of Inflammation

JF - Mediators of Inflammation

SN - 1466-1861

ER -