TY - JOUR T1 - Elevated expression of the NLRP3 inflammasome in neutrophilic asthma JF - European Respiratory Journal JO - Eur Respir J SP - 1067 LP - 1076 DO - 10.1183/09031936.00105013 VL - 43 IS - 4 AU - Jodie L. Simpson AU - Simon Phipps AU - Katherine J. Baines AU - Kevin M. Oreo AU - Lakshitha Gunawardhana AU - Peter G. Gibson Y1 - 2014/04/01 UR - http://erj.ersjournals.com/content/43/4/1067.abstract N2 - 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. The NLRP3 inflammasome may be a key regulator of neutrophilic airway inflammation in asthma through production of IL-1β http://ow.ly/t8HCe ER -