The role of pyroptosis in inflammatory diseases

Abstract

Programmed cell death has crucial roles in the physiological maturation of an organism, the maintenance of metabolism, and disease progression. Pyroptosis, a form of programmed cell death which has recently received much attention, is closely related to inflammation and occurs via canonical, non-canonical, caspase-3-dependent, and unclassified pathways. The pore-forming gasdermin proteins mediate pyroptosis by promoting cell lysis, contributing to the outflow of large amounts of inflammatory cytokines and cellular contents. Although the inflammatory response is critical for the body’s defense against pathogens, uncontrolled inflammation can cause tissue damage and is a vital factor in the occurrence and progression of various diseases. In this review, we briefly summarize the major signaling pathways of pyroptosis and discuss current research on the pathological function of pyroptosis in autoinflammatory diseases and sterile inflammatory diseases.

Age pigment lipofuscin causes oxidative stress, lysosomal dysfunction, and pyroptotic cell death

“…Previous studies reported lysosomal membrane permeabilization by iron and leakage of cathepsin D as an inducer of necrotic cell death 39 and release of cathepsin B into the cytosol as an activator of pyroptosis 40 . Traditionally incited by pathogen-associated molecular patterns (PAMPs), pyroptosis can also be spurred by elevated levels of ROS and lysosomal rupture 41, 42 . Remarkably, our observations regarding the activation of caspase 1 and the concomitant presence of inactive caspase 3 in fibroblasts subjected to lipofuscin treatment in combination with lysosomal rupture and elevated ROS concentrations, closely align with the early phase of pyroptosis.…”

B355252 Suppresses LPS-Induced Neuroinflammation in the Mouse Brain

“…The broad-range increases in cytokines could be the consequence of pyroptosis pathway activation or independence. Interleukins, TNF cytokines, and c-c and c-x chemokines could be released as part of an inflammatory response triggered by pyroptotic cell death [62][63][64][65]. Inhibiting TNF-α by CC-5013 has been shown to suppress pyroptosis signaling in the liver and kidneys through a caspase-1 independent pathway [66].…”

The NLRP3 inflammasome in viral infection (Review)

“…LRR has been involved in ligand-sensing and autoregulation. All three domains are involved in the protein interaction networks ( 7 ).…”

“…NLRP3 is known to respond to a variety of stimuli, including PAMPs, DAMPs and bacterial toxins. These PAMPs include fungi, such as Candida albicans and Saccharomyces cerevisiae ( 23 ); bacteria, including Staphylococcus aureus (S. aureus), Listeria monocytogenes and Neisseria gonorrhoeae ( 24 – 26 ); and viruses, such as Sendai, influenza, encephalomyocarditis viruses and adenovirus ( 7 , 27 – 29 ). In addition, several host-derived molecules, which are indicative of cellular injury or stress can also activate the NLRP3 inflammasome, including ATP released from necrotic cells, hyaluronan, glucose, monosodium urate, myeloid-β, skin irritants, imidazoquinoline compounds, silica, asbestos and alum ( Fig.…”