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Exploring the Involvement of NLRP3 and IL-1ß in Osteoarthritis of the Hand: Results from a Pilot Study.
Fioravanti, Antonella; Tenti, Sara; McAllister, Megan; Chemaly, Melody; Eakin, Amanda; McLaughlin, Joseph; Bjourson, Anthony J; Frati, Elena; McGilligan, Victoria; Cheleschi, Sara; Gibson, David S.
Afiliação
  • Fioravanti A; Rheumatology Unit, Department of Surgery, Medicine and Neurosciences, Le Scotte Hospital, Siena, Italy.
  • Tenti S; Rheumatology Unit, Department of Surgery, Medicine and Neurosciences, Le Scotte Hospital, Siena, Italy.
  • McAllister M; Northern Ireland Centre for Stratified Medicine, University of Ulster, Biomedical Sciences, Research Institute, Londonderry, UK.
  • Chemaly M; Northern Ireland Centre for Stratified Medicine, University of Ulster, Biomedical Sciences, Research Institute, Londonderry, UK.
  • Eakin A; Northern Ireland Centre for Stratified Medicine, University of Ulster, Biomedical Sciences, Research Institute, Londonderry, UK.
  • McLaughlin J; Northern Ireland Centre for Stratified Medicine, University of Ulster, Biomedical Sciences, Research Institute, Londonderry, UK.
  • Bjourson AJ; Northern Ireland Centre for Stratified Medicine, University of Ulster, Biomedical Sciences, Research Institute, Londonderry, UK.
  • Frati E; Rheumatology Unit, Department of Surgery, Medicine and Neurosciences, Le Scotte Hospital, Siena, Italy.
  • McGilligan V; Northern Ireland Centre for Stratified Medicine, University of Ulster, Biomedical Sciences, Research Institute, Londonderry, UK.
  • Cheleschi S; Rheumatology Unit, Department of Surgery, Medicine and Neurosciences, Le Scotte Hospital, Siena, Italy.
  • Gibson DS; Northern Ireland Centre for Stratified Medicine, University of Ulster, Biomedical Sciences, Research Institute, Londonderry, UK.
Mediators Inflamm ; 2019: 2363460, 2019.
Article em En | MEDLINE | ID: mdl-30983879
Hand osteoarthritis (HOA) includes different subsets; a particular and uncommon form is erosive HOA (EHOA). Interleukin- (IL-) 1ß plays a crucial role in the pathogenesis of osteoarthritis (OA); it is synthesized as an inactive precursor which requires the intervention of a cytosolic multiprotein complex, named inflammasome, for its activation. The aim of this study was to investigate the involvement of IL-1ß and the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome in patients with EHOA and nonerosive HOA (NEHOA) compared to healthy controls. In particular, we evaluated the gene expression of IL-1ß and NLRP3, the serum levels of IL-1ß, IL-6, IL-17, and tumor necrosis factor- (TNF-) α, and the protein levels of IL-1ß and NLRP3. We also assessed the relationships between IL-1ß and NLRP3 and clinical, laboratory, and radiological findings. Fifty-four patients with HOA (25 EHOA and 29 NEHOA) and 20 healthy subjects were included in the study. Peripheral blood mononuclear cell (PBMC) gene and protein expressions of IL-1ß and NLRP3 were quantified by quantitative real-time PCR and western blot. IL-1ß, IL-6, IL-17, and TNF-α serum levels were determined by ELISA. IL-1ß gene expression was significantly reduced (p = 0.0208) in EHOA compared to healthy controls. NLRP3 protein levels were significantly increased in the NEHOA group versus the control (p = 0.0063) and EHOA groups (p = 0.0038). IL-1ß serum levels were not significantly different across the groups; IL-6, IL-17, and TNF-α were not detectable in any sample. IL-1ß concentrations were negatively correlated with the Kellgren-Lawrence score in the whole population (r = -0.446; p = 0.0008) and in NEHOA (r = -0.608; p = 0.004), while IL-1ß gene expression was positively correlated with the number of joint swellings in the EHOA group (r = 0.512; p = 0.011). Taken together, our results, showing poorly detectable IL-1ß 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 the local level.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Osteoartrite / Articulação da Mão / Interleucina-1beta / Proteína 3 que Contém Domínio de Pirina da Família NLR Limite: Aged / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Osteoartrite / Articulação da Mão / Interleucina-1beta / Proteína 3 que Contém Domínio de Pirina da Família NLR Limite: Aged / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2019 Tipo de documento: Article