Role of NLRP3 Inflammasome in Airway Inflammation and Fibrosis

Abstract

The NLRP3 inflammasome is a critical component of the innate immune system that mediates caspase-1 activation and the secretion of proinflammatory cytokines IL-1β/IL-18 in response to microbial infection and cellular damage. Nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain 3 (NLRP3), one of the members of the NLR family, consists of NLRP3, the adaptor molecule, apoptosis-associated speck-like protein containing a caspase and recruitment domain (ASC) and an inflammatory caspase-1 that causes excessive inflammasome activation in respiratory diseases like asthma and could exacerbate the progression of asthma by considerably contributing to ECM accumulation and airway remodeling. NLRP3 is closely associated with airway inflammation and asthma exacerbations as endotoxin (lipopolysaccharide, LPS) is one of its activators present in the environment. Asthma is a complex immunological and inflammatory disease characterized by the presence of airway inflammation, airway wall remodeling and bronchial hyperresponsiveness (BHR). Symptomatic attacks of asthma can be caused by a myriad of situations, including allergens, infections, and pollutants, which cause the rapid aggravation of respiratory problems. The presence of LPS in the environment is positively correlated with the incidence of asthma and allergic diseases. In this chapter, we summarize our current understanding of the mechanisms of NLRP3 inflammasome activation by multiple signaling events in asthmatic exacerbations and their regulation.