Hypertonic saline induces inflammation in human macrophages through the NLRP1 inflammasome

Genes Immun. 2023 Oct;24(5):263-269. doi: 10.1038/s41435-023-00218-7. Epub 2023 Aug 12.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Inflammasomes*
  • Inflammation / metabolism
  • Interleukin-1beta
  • Macrophages / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein* / genetics
  • NLR Proteins / metabolism
  • Sodium Chloride / metabolism

Substances

  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Sodium Chloride
  • Interleukin-1beta
  • NLRP1 protein, human
  • NLR Proteins