Inflammasomes as therapeutic targets in human diseases

Abstract

Inflammasomes are protein complexes of the innate immune system that initiate inflammation in response to either exogenous pathogens or endogenous danger signals. Inflammasome multiprotein complexes are composed of three parts: a sensor protein, an adaptor, and pro-caspase-1. Activation of the inflammasome leads to the activation of caspase-1, which cleaves pro-inflammatory cytokines such as IL-1β and IL-18, leading to pyroptosis. Effectors of the inflammasome not only provide protection against infectious pathogens, but also mediate control over sterile insults. Aberrant inflammasome signaling has been implicated in the development of cardiovascular and metabolic diseases, cancer, and neurodegenerative disorders. Here, we review the role of the inflammasome as a double-edged sword in various diseases, and the outcomes can be either good or bad depending on the disease, as well as the genetic background. We highlight inflammasome memory and the two-shot activation process. We also propose the M- and N-type inflammation model, and discuss how the inflammasome pathway may be targeted for the development of novel therapy.

Emerging Role of LncRNA Regulation for NLRP3 Inflammasome in Diabetes Complications

“…Diabetes and its complications activate NLRP3 inflammasome through hyperglycemia, hypercholesterolemia, and hyperuricemia, resulting in a rise of IL-1β and IL-18 levels and inducing inflammatory response (Schroder et al, 2010). The current study revealed that reducing NLRP3 inflammasome activation can prevent and reduce diabetic complications (Ashrafizadeh et al, 2021;Li et al, 2021). As an upstream regulator of NLRP3 inflammasome, lncRNA can exert control over diabetes and its complications (Li et al, 2017b).…”

“…Increasing evidence demonstrates that NLRP3 inflammasome is implicated in developing diabetes and associated complications ( Schroder et al, 2010 ; Wada and Makino, 2016 ; Tang and Yiu, 2020 ; Li et al, 2021 ). Diabetes and its complications activate NLRP3 inflammasome through hyperglycemia, hypercholesterolemia, and hyperuricemia, resulting in a rise of IL-1β and IL-18 levels and inducing inflammatory response ( Schroder et al, 2010 ).…”

Probenecid-Blocked Pannexin-1 Channel Protects Against Early Brain Injury via Inhibiting Neuronal AIM2 Inflammasome Activation After Subarachnoid Hemorrhage

“…Inflammasomes are cytosolic multiprotein complexes that typically have three main components: a cytosolic pattern-recognition receptor, the enzyme caspase-1, and an adaptors ( 30 ). The activation of caspase-1 cleaved the inactive pro-IL-1β and pro-IL-18 into mature cytokines and induce a pro-inflammatory cell death, pyroptosis ( 5 , 31 ). An increasing number of evidence has shown that Z-VAD-FMK or AC-YVAD-CMK, caspase-1 inhibitors, could reduce inflammasome activation-mediated inflammatory response and neuronal cell death after stroke ( 32 – 34 ).…”

Local and Systemic Cytokine, Chemokine, and FGF Profile in Bacterial Chondronecrosis with Osteomyelitis (BCO)-Affected Broilers

“…Inflammasome complexes are a part of the innate immune system initiating inflammation. Their activation leads to the activation of caspase-1, which is responsible for the cleavage and subsequent activation of proinflammatory cytokines, such as IL-1β [56]. Its expression has been seen in the primary cells of myeloid and lymphoid origin as well as bone marrow and B cells and to be upregulated in chicken macrophages under inflammatory states [57,58].…”