Characterization and inhibition of inflammasome responses in severe and non-severe asthma.

Horvat, JC; Kim, RY; Weaver, N; Augood, C; Brown, AC; Donovan, C; Dupre, P; Gunawardhana, L; Mayall, JR; Hansbro, NG; Robertson, AAB; O'Neill, LAJ; Cooper, MA; Holliday, EG; Hansbro, PM; Gibson, PG

Characterization and inhibition of inflammasome responses in severe and non-severe asthma.

Horvat, JC Kim, RY Weaver, N Augood, C Brown, AC Donovan, C

Dupre, P Gunawardhana, L Mayall, JR Hansbro, NG Robertson, AAB O'Neill, LAJ Cooper, MA Holliday, EG Hansbro, PM Gibson, PG

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Publisher:: BMC
Publication Type:: Journal Article
Citation:: Respir Res, 2023, 24, (1), pp. 303
Issue Date:: 2023-12-04

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Field	Value	Language
dc.contributor.author	Horvat, JC
dc.contributor.author	Kim, RY
dc.contributor.author	Weaver, N
dc.contributor.author	Augood, C
dc.contributor.author	Brown, AC
dc.contributor.author	Donovan, C https://orcid.org/0000-0003-4558-329X
dc.contributor.author	Dupre, P
dc.contributor.author	Gunawardhana, L
dc.contributor.author	Mayall, JR
dc.contributor.author	Hansbro, NG
dc.contributor.author	Robertson, AAB
dc.contributor.author	O'Neill, LAJ
dc.contributor.author	Cooper, MA
dc.contributor.author	Holliday, EG
dc.contributor.author	Hansbro, PM
dc.contributor.author	Gibson, PG
dc.date.accessioned	2024-01-25T05:26:28Z
dc.date.available	2023-11-12
dc.date.available	2024-01-25T05:26:28Z
dc.date.issued	2023-12-04
dc.identifier.citation	Respir Res, 2023, 24, (1), pp. 303
dc.identifier.issn	1465-9921
dc.identifier.issn	1465-993X
dc.identifier.uri	http://hdl.handle.net/10453/174943
dc.description.abstract	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.
dc.format	Electronic
dc.language	eng
dc.publisher	BMC
dc.relation	http://purl.org/au-research/grants/nhmrc/APP1120252
dc.relation	http://purl.org/au-research/grants/nhmrc/1118973
dc.relation	http://purl.org/au-research/grants/nhmrc/1175134
dc.relation	http://purl.org/au-research/grants/nhmrc/1120252
dc.relation.ispartof	Respir Res
dc.relation.isbasedon	10.1186/s12931-023-02603-2
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	1102 Cardiorespiratory Medicine and Haematology, 1103 Clinical Sciences
dc.subject.classification	Respiratory System
dc.subject.classification	3201 Cardiovascular medicine and haematology
dc.subject.classification	3202 Clinical sciences
dc.subject.mesh	Humans
dc.subject.mesh	Male
dc.subject.mesh	Female
dc.subject.mesh	Inflammasomes
dc.subject.mesh	NLR Family, Pyrin Domain-Containing 3 Protein
dc.subject.mesh	Nigericin
dc.subject.mesh	Lipopolysaccharides
dc.subject.mesh	Leukocytes, Mononuclear
dc.subject.mesh	Interleukin-1beta
dc.subject.mesh	Asthma
dc.subject.mesh	Sulfonamides
dc.subject.mesh	Leukocytes, Mononuclear
dc.subject.mesh	Humans
dc.subject.mesh	Asthma
dc.subject.mesh	Sulfonamides
dc.subject.mesh	Nigericin
dc.subject.mesh	Lipopolysaccharides
dc.subject.mesh	Female
dc.subject.mesh	Male
dc.subject.mesh	Interleukin-1beta
dc.subject.mesh	Inflammasomes
dc.subject.mesh	NLR Family, Pyrin Domain-Containing 3 Protein
dc.subject.mesh	Humans
dc.subject.mesh	Male
dc.subject.mesh	Female
dc.subject.mesh	Inflammasomes
dc.subject.mesh	NLR Family, Pyrin Domain-Containing 3 Protein
dc.subject.mesh	Nigericin
dc.subject.mesh	Lipopolysaccharides
dc.subject.mesh	Leukocytes, Mononuclear
dc.subject.mesh	Interleukin-1beta
dc.subject.mesh	Asthma
dc.subject.mesh	Sulfonamides
dc.title	Characterization and inhibition of inflammasome responses in severe and non-severe asthma.
dc.type	Journal Article
utslib.citation.volume	24
utslib.location.activity	England
utslib.for	1102 Cardiorespiratory Medicine and Haematology
utslib.for	1103 Clinical Sciences
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Science
pubs.organisational-group	University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	University of Technology Sydney/Strength - CFI - Centre for Inflammation
utslib.copyright.status	open_access	*
dc.date.updated	2024-01-25T05:26:24Z
pubs.issue	1
pubs.publication-status	Published online
pubs.volume	24
utslib.citation.issue	1

Abstract:

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.

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http://hdl.handle.net/10453/174943