- Title
- Elevated expression of the NLRP3 inflammasome in neutrophilic asthma
- Creator
- Simpson, Jodie L.; Phipps, Simon; Baines, Katherine J.; Oreo, Kevin M.; Gunawardhana, Lakshitha; Gibson, Peter G.
- Relation
- European Respiratory Journal Vol. 43, Issue 4, p. 1067-1076
- Publisher Link
- http://dx.doi.org/10.1183/09031936.00105013
- Publisher
- European Respiratory Society
- Resource Type
- journal article
- Date
- 2014
- Description
- 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.
- Subject
- heterogeneous inflammatory airways disorder; elevated gene expression; NLRP3; neutrophilic asthma
- Identifier
- http://hdl.handle.net/1959.13/1064283
- Identifier
- uon:17510
- Identifier
- ISSN:0903-1936
- Language
- eng
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