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Elevated expression of the NLRP3 inflammasome in neutrophilic asthma.
- Source :
-
The European respiratory journal [Eur Respir J] 2014 Apr; Vol. 43 (4), pp. 1067-76. Date of Electronic Publication: 2013 Oct 17. - Publication Year :
- 2014
-
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.
- Subjects :
- Adult
Aged
Aged, 80 and over
Apoptosis
Case-Control Studies
Caspases metabolism
Female
Gene Expression Regulation
Humans
Immunohistochemistry
Inflammation
Interleukin-1beta metabolism
Macrophages cytology
Male
Middle Aged
Multivariate Analysis
NLR Family, Pyrin Domain-Containing 3 Protein
Neutrophils cytology
Nod2 Signaling Adaptor Protein metabolism
Protein Structure, Tertiary
Spirometry
Sputum metabolism
Toll-Like Receptors metabolism
Young Adult
Asthma metabolism
Carrier Proteins metabolism
Inflammasomes metabolism
Neutrophils metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1399-3003
- Volume :
- 43
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- The European respiratory journal
- Publication Type :
- Academic Journal
- Accession number :
- 24136334
- Full Text :
- https://doi.org/10.1183/09031936.00105013