Inflammasomes are multiprotein signaling platforms that form upon sensing microbe- or damage-associated molecular patterns. Upon their formation, caspase-1 is activated, leading to the processing of certain proinflammatory cytokines and the initiation of a special type of cell death, known as pyroptosis. Among known inflammasomes, NLRP3 takes on special importance because it appears to be a gen...

Hyperhomocysteinemia (HHcy) has been shown to promote vascular inflammation and atherosclerosis, but the underlying mechanisms remain largely unknown. The NLRP3 inflammasome has been identified as the cellular machinery responsible for activation of inflammatory processes. In this study, we hypothesized that the activation of NLRP3 inflammasomes contributes to HHcy-induced inflammation and athe...

BACKGROUND Activation of the NLRP3 inflammasome is associated with metabolic dysfunction, and intermittent fasting has been shown to improve clinical presentation of NLRP3 inflammasome-linked diseases. As mitochondrial perturbations, which function as a damage-associated molecular pattern, exacerbate NLRP3 inflammasome activation, we investigated whether fasting blunts inflammasome activation v...

While the molecular mechanisms promoting activation of the Nod-like Receptor (NLR) family member NLRP3 inflammasome are beginning to be defined, little is known about the mechanisms that regulate the NLRP3 inflammasome. Acute (up to 4 hours) LPS stimulation, followed by ATP is frequently used to activate the NLRP3 inflammasome in macrophages. Interestingly, we observed that the ability of LPS t...

Activation of cannabinoid receptor 2 (CB2R) ameliorates inflammation, but the underlying mechanism remains unclear. In the present study, we examined whether activation of CB2R could suppress the nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome. In peritoneal macrophages isolated from C57BL/6 mice, LPS/DSS challenge for 24 h increased the expression of the compon...

Activation of NLRP3 inflammasome is important for effective host defense against invading pathogen. Together with apoptosis-associated speck-like protein containing CARD domain (ASC), NLRP3 induces the cleavage of caspase-1 to facilitate the maturation of interleukin-1beta (IL-1β), an important pro-inflammatory cytokine. IL-1β subsequently plays critical roles in inflammatory responses by activ...

BACKGROUND The role of Foxo3a in the regulation of autophagy flux and activation of the NLRP3 inflammasome in KCs suffering from HFD conditions is unknown. RESULTS Up-regulation of Foxo3a restored autophagy flux and dampened the activation of the NLRP3 inflammasome in KCs stimulated with PA and LPS. In contrast, down-regulation of Foxo3a increased blockage of autophagy flux and promoted NLRP3...

The inflammasomes are multiprotein complexes sensing tissue damage and infectious agents to initiate innate immune responses. Different inflammasomes containing distinct sensor molecules exist. The NLRP3 inflammasome is unique as it detects a variety of danger signals. It has been reported that NLRP3 is recruited to mitochondria-associated endoplasmic reticulum membranes (MAMs) and is activated...

Growing evidence has shown that NLRP3 inflammasome activation promotes the development of tubularinterstitial inflammation and progression of renal injury. We previously found that mitochondrial dysfunction is a critical determinant for the activation of NLRP3 inflammasome in albumin-overload rats. Angiotensin (Ang) II plays an important role in mitochondrial homeostasis. Here, we investigated ...

BACKGROUND Emerging evidence indicates that NLRP3 inflammasome-induced inflammation plays a crucial role in the pathogenesis of depression. Thus, inhibition of NLRP3 inflammasome activation may offer a therapeutic benefit in the treatment of depression. Fluoxetine, a widely used antidepressant, has been shown to have potential antiinflammatory activity, but the underlying mechanisms remain obsc...