Department of Women's & Children's Health, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK.
Department of Respiratory Medicine, Alder Hey Children's NHS Foundation Trust Hospital, Liverpool, UK.
Genes Immun. 2023 Oct;24(5):263-269. doi: 10.1038/s41435-023-00218-7. Epub 2023 Aug 12.
Nebulized hypertonic saline (3-7%) is commonly used to increase mucociliary clearance in patients with chronic airway disease and/or virus infections. However, altered salt concentrations may contribute to inflammatory responses. The aim of this study was to investigate whether 500 mM NaCl (3%) triggers inflammation in human macrophages and identify the molecular mechanisms involved. NaCl-induced pyroptosis, IL-1β, IL-18 and ASC speck release were measured in primary human monocyte-derived macrophages. Treatment with the recombinant IL-1 receptor antagonist anakinra or the NLRP3 inhibitor MCC950 did not affect NaCl-mediated inflammasome assembly. Knock-down of NLRP1 expression, but not of NLRP3 and NLRC4, reduced NaCl-induced pyroptosis, pro-inflammatory cytokine and ASC speck release from human THP-1-derived macrophages. Data from this study suggest that 3% NaCl-induced inflammatory responses in human macrophages depend on NLRP1 and inflammasome assembly. Targeting inflammation in addition to inhalation with hypertonic saline may benefit patients with inflammatory airway disease.
雾化高渗盐水（3-7%）常用于增加慢性气道疾病和/或病毒感染患者的黏液纤毛清除率。然而，盐浓度的改变可能会引起炎症反应。本研究旨在探讨 500mM NaCl（3%）是否会引发人巨噬细胞的炎症，并确定涉及的分子机制。在原代人单核细胞衍生的巨噬细胞中测量 NaCl 诱导的细胞焦亡、IL-1β、IL-18 和 ASC 斑点释放。重组 IL-1 受体拮抗剂 anakinra 或 NLRP3 抑制剂 MCC950 的治疗并不影响 NaCl 介导的炎性小体组装。敲低 NLRP1 表达，但不敲低 NLRP3 和 NLRC4，可减少 3%NaCl 诱导的人 THP-1 衍生巨噬细胞的细胞焦亡、促炎细胞因子和 ASC 斑点释放。本研究的数据表明，3%NaCl 诱导的人巨噬细胞炎症反应依赖于 NLRP1 和炎性小体组装。除了吸入高渗盐水外，靶向炎症可能有益于炎症性气道疾病患者。
