Asthma is characterized by airway inflammation, airway hyperresponsiveness and airway remodelling. Uncontrolled airway inflammation or repeated asthma exacerbations can lead to airway remodelling, which cannot be reversed by current pharmacological treatment, and consequently lead to decline in lung function. Thus, it is critical to understand airway inflammation in asthma and infectious exacerbation. The inflammasome has emerged as playing a key role in innate immunity and inflammation. Upon ligand sensing, inflammasome components assemble and self-oligomerize, leading to caspase-1 activation and maturation of pro-IL-1β and pro-IL-18 into bioactive cytokines. These bioactive cytokines then play a pivotal role in the initiation and amplification of inflammatory processes. In addition to facilitating the proteolytic activation of IL-1β and IL-18, inflammasomes also participate in cell death through caspase-1-mediated pyroptosis. In this review, we describe the structure and function of the inflammasome and provide an overview of our current understanding of role of the inflammasome in airway inflammation. We focus on nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome as it is the best-characterized subtype shown expressed in airway and considered to play a key role in chronic airway diseases such as asthma.

Inflammasomes have emerged as playing key roles in inflammation and innate immunity. A growing body of evidence has suggested that the nucleotide-binding domain and leucine-rich repeat protein-3 (NLRP3) inflammasome is important in chronic airway diseases such as asthma and chronic obstructive pulmonary disease. Inflammasome activation results, in part, in pro-IL-1β processing and the secretion of the proinflammatory cytokine IL-1β. Because asthma exacerbations are associated with elevated concentrations of secreted IL-1β, we addressed whether the NLRP3 inflammasome is activated under in vitro conditions that mimic infectious exacerbations in asthma. Primary cultures of airway smooth muscle (ASM) cells were treated with infectious stimuli (mimicked using the Toll-like receptor-2 agonist Pam3CSK4, a synthetic bacterial lipopeptide). Whereas Pam3CSK4 robustly up-regulated ASM cytokine expression in response to TNF-α and significantly enhanced IL-1β mRNA expression, we were unable to detect IL-1β in the cell supernatants. Thus, IL-1β was not secreted and therefore was unable to act in an autocrine manner to promote the amplification of ASM inflammatory responses. Moreover, Toll-like receptor-2 ligation did not enhance NLRP3 or caspase-1 expression in ASM cells, and NLRP3 and caspase-1 protein were not present in the ASM layer of tracheal sections from human donors. In conclusion, these data demonstrate that the enhanced synthetic function of ASM cells, induced by infectious exacerbations of airway inflammation, is NLRP3 inflammasome-independent and IL-1β-independent. Activation of the NLRP3 inflammasome by invading pathogens may prove cell type-specific in exacerbations of airway inflammation in asthma.