期刊
MODERN RHEUMATOLOGY
卷 28, 期 3, 页码 513-517出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/14397595.2017.1369924
关键词
Caspase-1; gout; IL-1 beta; inflammasome; monosodium urate; TNF-alpha
类别
资金
- Japan Society for the Promotion of Science [C26461481]
Objective: Monosodium urate (MSU) has been shown to promote interleukin-1 (IL-1) secretion in human monocytes, but the priming signals for NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome pathway remains elusive. In this study, we investigated the role of Tumor necrosis factor-alpha (TNF-) on MSU-mediated IL-1 induction in human neutrophils.Methods: Human neutrophils were stimulated with MSU, in the presence or absence of TNF- priming. The cellular supernatants were analyzed for IL-1, IL-18, and caspase-1 by enzyme-linked immunosorbent assay (ELISA) methods. Pro-IL-1 mRNA expressions in human neutrophils were analyzed by real-time PCR method.Results: TNF- stimulation induced pro-IL-1 mRNA expression; however, MSU stimulation did not induce pro-IL-1 mRNA expression in human neutrophils. TNF- alone or MSU stimulation did not result in efficient IL-1 secretion in human neutrophils, whereas in TNF--primed neutrophils, MSU stimulation resulted in a marked IL-1 and IL-18 secretion. TNF--primed neutrophils secreted cleaved caspase-1 (p20), in response to MSU stimulation.Conclusion: Our data demonstrate that priming of human neutrophils with TNF- promotes uric acid-mediated IL-1 secretion in the absence of microbial stimulation. These findings provide insights into the neutrophils-mediated inflammatory processes in gouty arthritis.
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