title: Caspase-1 mediated interleukin-18 activation in neutrophils promotes the activity of rheumatoid arthritis in a NLRP3 inflammasome independent manner.
abstract: OBJECTIVE
  To investigate the role of NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome in the peripheral neutrophils in rheumatoid arthritis (RA).
  
  
  METHODS
  RA patients (n=48) and healthy controls (n=41) were enrolled and blood samples were collected for analysis. Protein expression of NLRP3 inflammasome components was detected by Western blot. Messenger RNA expression of NLRP3 inflammasome was detected by quantitative real-time reverse transcription-PCR. Sera levels of interleukin-1 beta (IL-1β) and interleukin-18 (IL-18) were detected by enzyme-linked immunosorbent assay (ELISA). Correlations among NLRP3 inflammasome activation, sera cytokines and RA disease activities were analyzed.
  
  
  RESULTS
  Neutrophil count was positively correlated with the 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP). In neutrophils, protein expression of NLRP3, apoptosis associated speck-like protein containing a CARD (ASC) and pro-caspase-1 was significantly decreased, while protein expression of activated caspase-1 was significantly increased and positively correlated with DAS28-CRP. Caspase-1 activation was positively correlated with serum level of IL-18 but not IL-1β. Messenger RNA expression of NLRP3 and ASC was also significantly decreased in RA patients. Interestingly, NLRP3 mRNA level was negatively correlated with DAS28-CRP.
  
  
  CONCLUSIONS
  Our results indicated that overactivated caspase-1 in neutrophils of RA was likely to mediate IL-18 activation and thus promote the progression of RA in a NLRP3 inflammasome independent manner.
authors.affiliation: Department of Rheumatology, Provincial Hospital affiliated to Shandong University, No. 324 Jingwu Road, Jinan, 250021 China; Department of Immunology, Shandong University School of Medicine, 44 Wenhua Xi Road, Jinan 250012, China.
authors.forename: Zhaowen
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Rheumatology, Provincial Hospital affiliated to Shandong University, No. 324 Jingwu Road, Jinan, 250021 China.
authors.forename: Jin
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of Rheumatology, Provincial Hospital affiliated to Shandong University, No. 324 Jingwu Road, Jinan, 250021 China; Department of Immunology, Shandong University School of Medicine, 44 Wenhua Xi Road, Jinan 250012, China.
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Yu
authors.affiliation: Department of Rheumatology, Provincial Hospital affiliated to Shandong University, No. 324 Jingwu Road, Jinan, 250021 China.
authors.forename: Qingrui
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Rheumatology, Provincial Hospital affiliated to Shandong University, No. 324 Jingwu Road, Jinan, 250021 China. Electronic address: yuanchaozhang@163.com.
authors.forename: Yuanchao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Immunology, Shandong University School of Medicine, 44 Wenhua Xi Road, Jinan 250012, China. Electronic address: hanlihui@sdu.edu.cn.
authors.forename: Lihui
authors.initials: L
authors.lastname: Han
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D020170:Caspase 1 / Q000276:immunology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D058847:Inflammasomes / Q000276:immunology*; D020382:Interleukin-18 / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000276:immunology*; D000070576:NLR Proteins / Q000276:immunology; D018375:Neutrophil Activation / Q000276:immunology; D009504:Neutrophils / Q000276:immunology*
chemical_list: D058847:Inflammasomes; D020382:Interleukin-18; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D000070576:NLR Proteins; C453881:NLRP3 protein, human; D020170:Caspase 1
keywords: Caspase-1; Disease activity; Interleukin-18; NLRP3; Neutrophils; Rheumatoid arthritis