國家衛生研究院 NHRI:Item 3990099045/12739
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    題名: Decoy receptor 3 promotes preosteoclast cell death via reactive oxygen species-induced fas ligand expression and the IL-1alpha/IL-1 receptor antagonist pathway
    其他題名: Decoy receptor 3 promotes preosteoclast cell death via reactive oxygen species-induced fas ligand expression and the IL-1α/IL-1 receptor antagonist pathway
    作者: Peng, YJ;Peng, CT;Lin, YH;Lin, GJ;Huang, SH;Chen, SJ;Sytwu, HK;Cheng, CP
    貢獻者: National Institute of Infectious Diseases and Vaccinology
    摘要: PURPOSE: Interleukin-1α (IL-1α) is a potent cytokine that plays a role in inflammatory arthritis and bone loss. Decoy receptor 3 (DCR3) is an immune modulator of monocytes and macrophages. The aim of this study was to investigate the mechanism of DCR3 in IL-1α-induced osteoclastogenesis. METHODS: We treated murine macrophages with DCR3 during receptor activator of nuclear factor kappa Β ligand- (RANKL-) plus IL-1α-induced osteoclastogenesis to monitor osteoclast formation by tartrate-resistant acid phosphatase (TRAP) staining. Osteoclast activity was assessed using a pit formation assay. The mechanisms of inhibition were studied by biochemical analyses, including RT-PCR, immunofluorescent staining, flow cytometry, an apoptosis assay, immunoblotting, and ELISA. RESULTS: DCR3 suppresses IL-1α-induced osteoclastogenesis in both primary murine bone marrow-derived macrophages (BMM) and RAW264.7 cells as it inhibits bone resorption. DCR3 induces RANKL-treated osteoclast precursor cells to express IL-1α, secretory IL-1ra (sIL-1ra), intracellular IL-1ra (icIL-1ra), reactive oxygen species (ROS), and Fas ligand and to activate IL-1α-induced interleukin-1 receptor-associated kinase 4 (IRAK4). The suppression of DCR3 during RANKL- or IL-1α-induced osteoclastogenesis may be due to the abundant secretion of IL-1ra, accumulation of ROS, and expression of Fas ligand in apoptotic osteoclast precursor cells. CONCLUSIONS: We concluded that there is an inhibitory effect of DCR3 on osteoclastogenesis via ROS accumulation and ROS-induced Fas ligand, IL-1α, and IL-1ra expression. Our results suggested that the upregulation of DCR3 in preosteoclasts might be a therapeutic target in inflammatory IL-1α-induced bone resorption.
    日期: 2020-06-10
    關聯: Mediators of Inflammation. 2020 Jun 10;2020:Article number 1237281.
    Link to: http://dx.doi.org/10.1155/2020/1237281
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0962-9351&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000544593100001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85087131408
    顯示於類別:[司徒惠康] 期刊論文

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