Elevated expression of the NLRP3 inflammasome in neutrophilic asthma

Simpson, Jodie L., Phipps, Simon, Baines, Katherine J., Oreo, Kevin M., Gunawardhana, Lakshitha and Gibson, Peter G. (2014) Elevated expression of the NLRP3 inflammasome in neutrophilic asthma. European Respiratory Journal, 43 4: 1067-1076. doi:10.1183/09031936.00105013

Author Simpson, Jodie L.
Phipps, Simon
Baines, Katherine J.
Oreo, Kevin M.
Gunawardhana, Lakshitha
Gibson, Peter G.
Title Elevated expression of the NLRP3 inflammasome in neutrophilic asthma
Journal name European Respiratory Journal   Check publisher's open access policy
ISSN 1399-3003
Publication date 2014-01-01
Year available 2013
Sub-type Article (original research)
DOI 10.1183/09031936.00105013
Open Access Status Not yet assessed
Volume 43
Issue 4
Start page 1067
End page 1076
Total pages 10
Place of publication Lausanne, Switzerland
Publisher European Respiratory Society
Language eng
Abstract Asthma is a heterogeneous inflammatory airways disorder where interleukin (IL)-1β is thought to be a key mediator, especially in the neutrophilic subtype of asthma. The generation of active IL-1β requires proteolytic cleavage typically mediated through the formation of a caspase-1-containing inflammasome. This study hypothesised that an IL-1β endotype associated with the nucleotide-binding domain, leucine-rich repeat-containing family protein (NLRP)3/apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC)/caspase-1 inflammasome is characteristic of patients with the neutrophilic subtype of asthma. Participants with asthma (n=85) and healthy controls (n=27) underwent clinical assessment, spirometry and sputum induction. Sputum was processed for differential cell count, gene expression and protein mediators. NLRP3 and caspase-1 expression was also determined by immunocytochemistry. Sputum macrophages were isolated (n=8) and gene expression of NLRP3 and IL-1β determined. There was significantly elevated gene expression of NLRP3, caspase-1, caspase-4, caspase-5 and IL-1β in participants with neutrophilic asthma. Protein levels of IL-1β were significantly higher in those with neutrophilic asthma and correlated with sputum IL-8 levels. Sputum macrophages, as well as sputum neutrophils in neutrophilic asthma, expressed NLRP3 and caspase-1 protein. NLRP3 inflammasome is upregulated in neutrophilic asthma and may regulate the inflammation process observed in this asthma phenotype through production of IL-1β. Copyright
Keyword Respiratory System
Respiratory System
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 631020
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Biomedical Sciences Publications
School of Chemistry and Molecular Biosciences
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