Hypertonic saline induces inflammation in human macrophages through the NLRP1 inflammasome.

Sposito, Francesca ORCID: 0009-0007-0272-0318, Northey, Sarah, Charras, Amandine ORCID: 0000-0001-6760-5459, McNamara, Paul S ORCID: 0000-0002-7055-6034 and Hedrich, Christian M ORCID: 0000-0002-1295-6179 (2023) Hypertonic saline induces inflammation in human macrophages through the NLRP1 inflammasome. Genes and immunity, 24 (5). pp. 263-269.

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Official URL: http://dx.doi.org/10.1038/s41435-023-00218-7

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.

Item Type:	Article
Uncontrolled Keywords:	Macrophages, Humans, Inflammation, Sodium Chloride, Interleukin-1beta, Inflammasomes, NLR Family, Pyrin Domain-Containing 3 Protein, NLR Proteins
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences
Depositing User:	Symplectic Admin
Date Deposited:	22 Aug 2023 09:43
Last Modified:	09 Dec 2023 02:10
DOI:	10.1038/s41435-023-00218-7
Open Access URL:	https://doi.org/10.1038/s41435-023-00218-7
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3172288