Zhaowen Yang1, Jin Cao2, Chengcheng Yu1, Qingrui Yang2, Yuanchao Zhang3, Lihui Han4. 1. 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. 2. Department of Rheumatology, Provincial Hospital affiliated to Shandong University, No. 324 Jingwu Road, Jinan, 250021 China. 3. Department of Rheumatology, Provincial Hospital affiliated to Shandong University, No. 324 Jingwu Road, Jinan, 250021 China. Electronic address: yuanchaozhang@163.com. 4. Department of Immunology, Shandong University School of Medicine, 44 Wenhua Xi Road, Jinan 250012, China. Electronic address: hanlihui@sdu.edu.cn.
Abstract
OBJECTIVES: 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.
OBJECTIVES: To investigate the role of NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome in the peripheral neutrophils in rheumatoid arthritis (RA). METHODS:RApatients (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 RApatients. 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: David B Bartlett; Margery A Connelly; Hiba AbouAssi; Lori A Bateman; K Noelle Tune; Janet L Huebner; Virginia B Kraus; Deborah A Winegar; James D Otvos; William E Kraus; Kim M Huffman Journal: Arthritis Res Ther Date: 2016-04-12 Impact factor: 5.156