NLRP3 inflammasome in digestive diseases: From mechanism to therapy

Qiang, Rui; Li, Yanbo; Dai, Xin-Can; Lv, Wenliang

doi:10.3389/fimmu.2022.978190

Cited by 8 publications

(3 citation statements)

References 243 publications

(252 reference statements)

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“…Digestive system diseases, including inflammatory bowel disease (IBD), diverticulitis, colorectal cancer, and liver diseases, arise primarily through the interplay of genetic and environmental influences. There conditions pose a formidable challenge to human health and have become a growing global burden [ 155 , 156 ]. Oxidative stress is a major contributor to gastrointestinal mucosal diseases, with the overproduction of ROSs implicated in the development of these conditions [ 157 , 158 ].…”

Section: Research Progress In Gpx3 and Non-neoplastic Diseasesmentioning

confidence: 99%

Insights into the Role of Glutathione Peroxidase 3 in Non-Neoplastic Diseases

Zhang,

Liao,

Lin

et al. 2024

Biomolecules

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Reactive oxygen species (ROSs) are byproducts of normal cellular metabolism and play pivotal roles in various physiological processes. Disruptions in the balance between ROS levels and the body’s antioxidant defenses can lead to the development of numerous diseases. Glutathione peroxidase 3 (GPX3), a key component of the body’s antioxidant system, is an oxidoreductase enzyme. GPX3 mitigates oxidative damage by catalyzing the conversion of hydrogen peroxide into water. Beyond its antioxidant function, GPX3 is vital in regulating metabolism, modulating cell growth, inducing apoptosis and facilitating signal transduction. It also serves as a significant tumor suppressor in various cancers. Recent studies have revealed aberrant expression of GPX3 in several non-neoplastic diseases, associating it with multiple pathological processes. This review synthesizes the current understanding of GPX3 expression and regulation, highlighting its extensive roles in noncancerous diseases. Additionally, this paper evaluates the potential of GPX3 as a diagnostic biomarker and explores emerging therapeutic strategies targeting this enzyme, offering potential avenues for future clinical treatment of non-neoplastic conditions.

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Section: Research Progress In Gpx3 and Non-neoplastic Diseasesmentioning

confidence: 99%

Insights into the Role of Glutathione Peroxidase 3 in Non-Neoplastic Diseases

Zhang,

Liao,

Lin

et al. 2024

Biomolecules

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“…NLRP3 inflammasome formation is believed to be pro-tumorigenic with regards to PDAC (reviewed in [5]). PDAC tumor cells can produce IL-1β through NLRP3 inflammasome activation [18], and this is essential to the establishment of the tumor microenvironment [19]. However, the IL-1β protein is often undetected in PDAC cell lines grown in vitro and as organoids but robustly produced by primary PDAC tumors [17].…”

Section: Introductionmentioning

confidence: 99%

The Co-Localization of NLRP3 and ASC Specks Does Not Automatically Entail NLRP3 Inflammasome Functionality in PDAC Cell Lines

Lindholm,

Herring,

Faresjö

et al. 2024

IJTM

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The NLRP3 inflammasome is an important mediator of the host inflammatory response, and downregulation of inflammation is important in cancer treatment. Here, we investigated four different pancreatic ductal adenocarcinoma (PDAC) cell lines, AsPC-1, BxPC-3, CFPAC-1 and Panc-1, with regards to NLRP3 inflammasome formation and cytokine secretion. ASC specks were observed in all the cell lines investigated, but AsPC-1 was the only cell-line with the co-localization of anti-ASC and anti-NLRP3 and spontaneously formed multiple NLRP3 inflammasomes per cell. The co-localization of NLRP3 and ASC was not accompanied by IL-1β release nor significant IL-18 release. BxPC-3 displayed relatively high expression of the inflammasome-related genes IL1B and CASP1 and had the highest levels of IL1β and IL18 secretion and the highest amount of ASC. The inflammasome-associated genes IL18 and PYCARD were up-regulated in the PDAC primary tumors compared to normal tissue, and high PDAC tumor expression of IL18, CASP1 and PYCARD correlated with low patient survival. We have shown that PDAC cell lines display significant variations in their inflammasome-related gene expression and readouts. We conclude that spontaneous ASC speck formation is possible in PDAC cells and that multiple NLRP3 inflammasomes are formed spontaneously in AsPC-1 cells but that the co-localization of NLRP3 and ASC specks does not automatically entail inflammasome function.

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“…Despite its protective function, inflammasome activation must be tightly regulated, since, if prolonged, it could aggravate the outcome of several inflammation-driven diseases, such as cryopyrin-associated periodic syndrome, arthritis, atherosclerosis, type 2 diabetes, Alzheimer's disease, inflammatory bowel diseases (IBDs), including Crohn’s disease (CD), ulcerative colitis (UC), and cancer [ 8 ], whose onset and development is mostly a consequence of multiple risk factors. Among inflammasomes, the NLRP3 pathway is the best studied today, featuring both protective and pathogenic abilities within the gastrointestinal (GI) tract [ 9 ]. In this review we aim to summarize the current knowledge of the patho-physiological aspects of NLRP3 inflammasome activation in the GI tract and the potential therapeutic approaches considered nowadays as alternatives to conventional protocols in patients with inflammatory-driven GI disorders, laying particular emphasis on IBD and cancer.…”

Section: Introductionmentioning

confidence: 99%

The ‘speck’-tacular oversight of the NLRP3-pyroptosis pathway on gastrointestinal inflammatory diseases and tumorigenesis

Arrè,

Scialpi,

Centonze

et al. 2023

J Biomed Sci

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The NLRP3 inflammasome is an intracellular sensor and an essential component of the innate immune system involved in danger recognition. An important hallmark of inflammasome activation is the formation of a single supramolecular punctum, known as a speck, per cell, which is the site where the pro-inflammatory cytokines IL-1β and IL-18 are converted into their bioactive form. Speck also provides the platform for gasdermin D protein activation, whose N-terminus domain perforates the plasma membrane, allowing the release of mature cytokines alongside with a highly inflammatory form of cell death, namely pyroptosis. Although controlled NLRP3 inflammasome-pyroptosis pathway activation preserves mucosal immunity homeostasis and contributes to host defense, a prolonged trigger is deleterious and could lead, in genetically predisposed subjects, to the onset of inflammatory bowel disease, including Crohn's disease and ulcerative colitis, as well as to gastrointestinal cancer. Experimental evidence shows that the NLRP3 inflammasome has both protective and pathogenic abilities. In this review we highlight the impact of the NLRP3-pyroptosis axis on the pathophysiology of the gastrointestinal tract at molecular level, focusing on newly discovered features bearing pro- and anti-inflammatory and neoplastic activity, and on targeted therapies tested in preclinical and clinical trials.

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NLRP3 inflammasome in digestive diseases: From mechanism to therapy

Cited by 8 publications

References 243 publications

Insights into the Role of Glutathione Peroxidase 3 in Non-Neoplastic Diseases

Insights into the Role of Glutathione Peroxidase 3 in Non-Neoplastic Diseases

The Co-Localization of NLRP3 and ASC Specks Does Not Automatically Entail NLRP3 Inflammasome Functionality in PDAC Cell Lines

The ‘speck’-tacular oversight of the NLRP3-pyroptosis pathway on gastrointestinal inflammatory diseases and tumorigenesis

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