The Interplay between Autophagy and NLRP3 Inflammasome in Ischemia/Reperfusion Injury

Abstract

Ischemia/reperfusion (I/R) injury is characterized by a limited blood supply to organs, followed by the restoration of blood flow and reoxygenation. In addition to ischemia, blood flow recovery can also lead to very harmful injury, especially inflammatory injury. Autophagy refers to the transport of cellular materials to the lysosomes for degradation, leading to the conversion of cellular components and offering energy and macromolecular precursors. It can maintain the balance of synthesis, decomposition and reuse of the intracellular components, and participate in many physiological processes and diseases. Inflammasomes are a kind of protein complex. Under physiological and pathological conditions, as the cellular innate immune signal receptors, inflammasomes sense pathogens to trigger an inflammatory response. TheNLRP3 inflammasome is the most deeply studied inflammasome and is composed of NLRP3, the adaptor apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and pro-caspase-1. Its activation triggers the cleavage of pro-interleukin (IL)-1β and pro-IL-18 mediated by caspase-1 and promotes a further inflammatory process. Studies have shown that autophagy and the NLRP3 inflammasome play an important role in the process of I/R injury, but the relevant mechanisms have not been fully explained, especially how the interaction between autophagy and the NLRP3 inflammasome participates in I/R injury, which remains to be further studied. Therefore, we reviewed the recent studies about the interplay between autophagy and the NLRP3 inflammasome in I/R injury and analyzed the mechanisms to provide the theoretical references for further research in the future.

Myocardial injury: where inflammation and autophagy meet

“…NLRP3 inflammasome activation, lysosomal dysfunction and impaired autophagic flux play critical roles in the pathophysiology of I/R. In recent years, it has been found that macrophage autophagy plays a key role in NLRP3 activation during I/R [ 53 ]. In macrophages, lysosomes are at the center of key cellular processes that activate inflammasomes [ 54 , 55 ].…”

The Role of Pyroptosis and Autophagy in Ischemia Reperfusion Injury

“…In recent years, more and more evidence demonstrates that dysfunctional autophagy is related with many diseases, including ischemia/reperfusion injury. However, the related mechanisms are not fully clear [ 35 , 36 , 37 ].…”

The effects of sugammadex on gastric ischemia-reperfusion injury in rats: Biochemical and histopathological evaluation

“…Reperfusion also provides abundant reoxygenation to ischemic tissue with rebbleeding (Suleyman and Ozcicek 2020). Therefore, ischemia/ reperfusion (I/R) is characterized by interruption of blood flow to organs followed by restoration of blood flow and reoxygenation (Lv et al 2021). Some mediators and cytokines that occur during the I/R process can cause a physiopathological process defined as secondary tissue injury.…”