NLRP3 inflammasome as a novel target for cystic fibrosis treatment

Abstract

Abstract Background Inflammasomes are intracellular multiprotein complexes that sense danger signals from damaged cells and pathogens and assemble to mediate caspase-1 activation, which results in the proteolytic cleavage of pro-IL-1β and IL-18 into bioactive forms. The NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is a critical component of the innate immune system that mediates caspase-1 activation and secretion of the proinflammatory cytokines IL-1β/IL-18 in response to disturbances in cellular homeostasis caused by microbial infections and cellular damage. Main body of abstract The NLRP3 inflammasome is associated with various inflammatory disorders, including Alzheimer’s disease, diabetes, and atherosclerosis. In recent years, NLRP3 inflammasome has also been implicated in inflammation in cystic fibrosis. The differentiation of pro-IL-1β–IL-1β, an active cytokine, is mediated by neutrophil expression of the NLRP3 inflammasome. Furthermore, it maintains a cytokine storm in the lungs during the pathogenesis of CF. Short conclusion This review highlights neutrophil metabolic reprogramming characterized by the Warburg effect, NLRP3-mediated inflammation in cystic fibrosis, and its inhibition as a potential therapeutic strategy.