Inflammasomes in the Pathophysiology of Kidney Diseases

The inflammasome is a complex of proteins in the cytoplasm that consists of three main components: a sensor protein (receptor), an adapter protein and caspase-1. Inflammasomes are the critical components of innate immunity and have been gradually recognized as a critical mediator in various autoimmune diseases; also, their role in chronic kidney disease and acute kidney injury has been gradually accepted.

Inflammasomes triggered by infectious or sterile injuries transfer proinflammatory mediators into mature ones through innate danger-signaling platforms. Information on inflammasomes in kidney disease will help to uncover the underlying mechanisms of nephropathy and provide novel therapeutic targets in the future.

The inflammasomes can be activated by a series of exogenous and endogenous stimuli, including pathogen-and danger-associated molecular patterns released from or caused by damaged cells. The NACHT, LRR and PYD domain-containing protein 3 (NLRP3) in the kidney exerts its effect not only by the 'canonical' pathway of IL-1β and IL-18 secretion but also by 'noncanonical' pathways, such as tumor growth factor-β signaling, epithelial-mesenchymal transition and fibrosis. In both clinical and experimental data, the NLRP3 inflammasome was reported to be involved in the pathogenesis of chronic kidney disease and acute kidney injury. However, the underlying mechanisms are not fully understood. Therapies targeting the activation of the NLRP3 inflammasome or blocking its downstream effectors appear attractive for the pursuit of neuropathy treatments.