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Vasoactive intestinal peptide suppresses the NLRP3 inflammasome activation in lipopolysaccharide-induced acute lung injury mice and macrophages.

血管活性肠肽抑制脂多糖诱导的急性肺损伤小鼠和巨噬细胞中 NLRP3 炎症小体的活化。

  • 影响因子:3.78
  • DOI:10.1016/j.biopha.2019.109596
  • 作者列表:"Zhou Y","Zhang CY","Duan JX","Li Q","Yang HH","Sun CC","Zhang J","Luo XQ","Liu SK
  • 发表时间:2020-01-01
Abstract

:Vasoactive intestinal peptide (VIP) is a neuropeptide that exerts anti-inflammatory functions. We have reported that VIP mediated by lentivirus attenuates acute lung injury (ALI) in lipopolysaccharide (LPS)-induced murine model. However, the exact role of VIP in uncontrolled inflammation during ALI is largely unknown. Accumulating evidence indicates that the NLRP3 inflammasome has a critical role during ALI. In this study, we investigated the effects of VIP on the activation of NLRP3 inflammasome during the development of ALI in mice. Seven days after the intratracheal injection of VIP-lentivirus, a murine ALI model was induced by intratracheal injection of LPS. VIP-lentivirus significantly reduced the expression of NLRP3 inflammasome components in lung tissue, including NLRP3, pro-caspase-1, pro-IL-1β, and pro-IL-18. VIP-lentivirus also inhibited the formation of caspase-1 p10 and the maturation of IL-1β and IL-18. In vitro, exogenous VIP pre-treatment inhibited the priming of NLRP3 inflammasome in murine primary peritoneal macrophages, indicated by down-regulation of expression of NLRP3 inflammasome components. VIP pre-treatment effectively prevented the LPS-induced degradation of I-κB and the synthesis of the downstream of NF-κB, including TNF-α and IL-17A. Furthermore, VIP pre-treatment pronouncedly suppressed the autoproteolysis of caspase-1 and the secretion of IL-1β and IL-18 induced by LPS plus ATP in macrophages. In addition, VIP inhibited the generation of reactive oxygen species in macrophages by decreasing NOX1 and NOX2 expression. These findings illustrate one mechanism that VIP attenuates ALI induced by LPS through inhibiting the activation of the NLRP3 inflammasome and encourage further studies assessing the therapeutic potential of VIP to ALI.

摘要

: 血管活性肠肽 (VIP) 是一种发挥抗炎功能的神经肽。我们报道了慢病毒介导的 VIP 可减轻脂多糖 (LPS) 诱导的小鼠急性肺损伤 (ALI)。然而,VIP 在 ALI 过程中不受控制的炎症中的确切作用在很大程度上是未知的。越来越多的证据表明,NLRP3 炎症小体在 ALI 过程中具有关键作用。在本研究中,我们研究了 VIP 对小鼠 ALI 发育过程中 NLRP3 炎症小体激活的影响。气管内注射 VIP-慢病毒后 7 天,通过气管内注射 LPS 诱导小鼠 ALI 模型。VIP-慢病毒显著降低肺组织中 NLRP3 炎性体成分的表达,包括 NLRP3 、 pro-caspase-1 、 pro-il-1 β 和 pro-IL-18。VIP-慢病毒也抑制 caspase-1 p10 的形成和 il-1 β 和 IL-18 的成熟。在体外,外源性 VIP 预处理抑制小鼠原代腹腔巨噬细胞 NLRP3 炎性体的启动,表现为 NLRP3 炎性体成分表达下调。VIP 预处理有效地阻止了 LPS 诱导的 I-κ b 降解和 NF-κ b 下游的合成,包括 TNF-α 和 IL-17A。此外,VIP 预处理可明显抑制 LPS 加 ATP 诱导的巨噬细胞 caspase-1 自身蛋白酶解及 il-1 β 和 IL-18 的分泌。此外,VIP 通过降低 NOX1 和 NOX2 表达抑制巨噬细胞内活性氧的生成。这些发现说明了 VIP 通过抑制 NLRP3 炎症小体的激活减轻 LPS 诱导的 ALI 的一种机制,并鼓励进一步研究评估 VIP 对 ALI 的治疗潜力。

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影响因子:3.94
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DOI:10.1016/j.taap.2019.114847
作者列表:["Bernstein DM","Toth B","Rogers RA","Kling DE","Kunzendorf P","Phillips JI","Ernst H"]

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