- Title
- Characterization and inhibition of inflammasome responses in severe and non-severe asthma
- Creator
- Horvat, Jay C.; Kim, Richard Y.; Weaver, Natasha; Augood, Christopher; Brown, Alexandra C.; Donovan, Chantal; Dupre, Pierrick; Gunawardhana, Lakshitha; Mayall, Jemma R.; Hansbro, Nicole G.; Robertson, Avril A. B.; O'Neill, Luke A. J.; Cooper, Matthew A.; Holliday, Elizabeth G.; Hansbro, Philip M.; Gibson, Peter G.
- Relation
- NHMRC.1120252 http://purl.org/au-research/grants/nhmrc/1120252
- Relation
- Respiratory Research Vol. 24, Issue 1, no. 303
- Publisher Link
- http://dx.doi.org/10.1186/s12931-023-02603-2
- Publisher
- BioMed Central
- Resource Type
- journal article
- Date
- 2023
- Description
- Background: Increased airway NLRP3 inflammasome-mediated IL-1β responses may underpin severe neutrophilic asthma. However, whether increased inflammasome activation is unique to severe asthma, is a common feature of immune cells in all inflammatory types of severe asthma, and whether inflammasome activation can be therapeutically targeted in patients, remains unknown. Objective: To investigate the activation and inhibition of inflammasome-mediated IL-1β responses in immune cells from patients with asthma. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from patients with non-severe (n = 59) and severe (n = 36 stable, n = 17 exacerbating) asthma and healthy subjects (n = 39). PBMCs were stimulated with nigericin or lipopolysaccharide (LPS) alone, or in combination (LPS + nigericin), with or without the NLRP3 inhibitor MCC950, and the effects on IL-1β release were assessed. Results: PBMCs from patients with non-severe or severe asthma produced more IL-1β in response to nigericin than those from healthy subjects. PBMCs from patients with severe asthma released more IL-1β in response to LPS + nigericin than those from non-severe asthma. Inflammasome-induced IL-1β release from PBMCs from patients with severe asthma was not increased during exacerbation compared to when stable. Inflammasome-induced IL-1β release was not different between male and female, or obese and non-obese patients and correlated with eosinophil and neutrophil numbers in the airways. MCC950 effectively suppressed LPS-, nigericin-, and LPS + nigericin-induced IL-1β release from PBMCs from all groups. Conclusion: An increased ability for inflammasome priming and/or activation is a common feature of systemic immune cells in both severe and non-severe asthma, highlighting inflammasome inhibition as a universal therapy for different subtypes of disease.
- Subject
- asthma; severe asthma; NLRP3 inflammasome; IL-1β; inflammasome inhibition; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1501017
- Identifier
- uon:55056
- Identifier
- ISSN:1465-993X
- Rights
- © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecom-mons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
- Language
- eng
- Full Text
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