期刊
EUROPEAN RESPIRATORY JOURNAL
卷 43, 期 4, 页码 1067-1076出版社
EUROPEAN RESPIRATORY SOC JOURNALS LTD
DOI: 10.1183/09031936.00105013
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资金
- National Health and Medical Research Council (NHMRC) (Canberra, Australia) [631020]
- Australian Respiratory Council
- NHMRC
Asthma is a heterogeneous inflammatory airways disorder where interleukin (IL)-1 beta is thought to be a key mediator, especially in the neutrophilic subtype of asthma. The generation of active IL-1 beta requires proteolytic cleavage typically mediated through the formation of a caspase-1-containing inflammasome. This study hypothesised that an IL-1 beta 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-1 beta determined. There was significantly elevated gene expression of NLRP3, caspase-1, caspase-4, caspase-5 and IL-1 beta in participants with neutrophilic asthma. Protein levels of IL-1 beta 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-1 beta.
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