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NLRP3 inflammasome: from a danger signal sensor to a regulatory node of oxidative stress and inflammatory diseases.

Abderrazak A, Syrovets T, Couchie D, El Hadri K, Friguet B, Simmet T, Rouis M - Redox Biol (2015)

Bottom Line: We have reported mutations in NLRP3 that were found to be associated with certain diseases.In addition, we have reviewed the functional link between NLRP3 inflammasome, the regulator of cellular redox status Trx/TXNIP complex, endoplasmic reticulum stress and the pathogenesis of diseases such as type 2 diabetes.Finally, we have provided data on NLRP3 inflammasome, as a critical regulator involved in the pathogenesis of obesity and cardiovascular diseases.

View Article: PubMed Central - PubMed

Affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR 8256, Biological Adaptation and Ageing - IBPS, F-75005 Paris, France; CNRS-UMR 8256, F-75005 Paris, France; Inserm U1164, F-75005 Paris, France.

No MeSH data available.


Related in: MedlinePlus

Inflammasome is a central player in the induction of β-cell death and T2DM progression. Chronic exposure of pancreatic β-cells to elevated concentrations of glucose promotes TXNIP expression, endoplasmic reticulum stress and accumulation of dysfunctional mitochondria leading to intracellular ROS accumulation. ROS generation drives NLRP3 activation in a TXNIP-dependent manner. However, ER activation pathway(s) remain poorly understood. IAPP is deposited in pancreas and quickly taken up by macrophages. 1. mmLDL primes cells through TLR4 signaling and 2. IAPP specifically activates NLRP3 inflammasome and pro-IL-1β cleavage. IL1-β signaling induces a local proinflammatory environment through activation of other chemotactic factors and immune cell infiltration that aggravates β-cell failure.
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f0020: Inflammasome is a central player in the induction of β-cell death and T2DM progression. Chronic exposure of pancreatic β-cells to elevated concentrations of glucose promotes TXNIP expression, endoplasmic reticulum stress and accumulation of dysfunctional mitochondria leading to intracellular ROS accumulation. ROS generation drives NLRP3 activation in a TXNIP-dependent manner. However, ER activation pathway(s) remain poorly understood. IAPP is deposited in pancreas and quickly taken up by macrophages. 1. mmLDL primes cells through TLR4 signaling and 2. IAPP specifically activates NLRP3 inflammasome and pro-IL-1β cleavage. IL1-β signaling induces a local proinflammatory environment through activation of other chemotactic factors and immune cell infiltration that aggravates β-cell failure.

Mentions: While extensive study regarding the important role of TXNIP during hyperglycemia was reported; the role of TXNIP in inflammasome NLRP3 activation and IL-1β release requires further investigations to clearly highlight its implication. It has been shown that IL-1β signals in an autocrine and/or paracrine manner triggering β-cells dysfunction. Furthermore, it aggravates the local inflammatory environment through the secretion of other proinflammatory cytokines and chemotactic factors that drive infiltration of immune cells into pancreatic islets [106]. Elevated levels of glucose induce expression of TXNIP leading to an enhanced production of IL-1β in pancreatic islets [100] as well as human and mouse adipose tissue [107], but not in macrophages [100]. The role of the NLRP3 inflammasome in β-cell dysfunction is illustrated in Fig. 4.


NLRP3 inflammasome: from a danger signal sensor to a regulatory node of oxidative stress and inflammatory diseases.

Abderrazak A, Syrovets T, Couchie D, El Hadri K, Friguet B, Simmet T, Rouis M - Redox Biol (2015)

Inflammasome is a central player in the induction of β-cell death and T2DM progression. Chronic exposure of pancreatic β-cells to elevated concentrations of glucose promotes TXNIP expression, endoplasmic reticulum stress and accumulation of dysfunctional mitochondria leading to intracellular ROS accumulation. ROS generation drives NLRP3 activation in a TXNIP-dependent manner. However, ER activation pathway(s) remain poorly understood. IAPP is deposited in pancreas and quickly taken up by macrophages. 1. mmLDL primes cells through TLR4 signaling and 2. IAPP specifically activates NLRP3 inflammasome and pro-IL-1β cleavage. IL1-β signaling induces a local proinflammatory environment through activation of other chemotactic factors and immune cell infiltration that aggravates β-cell failure.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4315937&req=5

f0020: Inflammasome is a central player in the induction of β-cell death and T2DM progression. Chronic exposure of pancreatic β-cells to elevated concentrations of glucose promotes TXNIP expression, endoplasmic reticulum stress and accumulation of dysfunctional mitochondria leading to intracellular ROS accumulation. ROS generation drives NLRP3 activation in a TXNIP-dependent manner. However, ER activation pathway(s) remain poorly understood. IAPP is deposited in pancreas and quickly taken up by macrophages. 1. mmLDL primes cells through TLR4 signaling and 2. IAPP specifically activates NLRP3 inflammasome and pro-IL-1β cleavage. IL1-β signaling induces a local proinflammatory environment through activation of other chemotactic factors and immune cell infiltration that aggravates β-cell failure.
Mentions: While extensive study regarding the important role of TXNIP during hyperglycemia was reported; the role of TXNIP in inflammasome NLRP3 activation and IL-1β release requires further investigations to clearly highlight its implication. It has been shown that IL-1β signals in an autocrine and/or paracrine manner triggering β-cells dysfunction. Furthermore, it aggravates the local inflammatory environment through the secretion of other proinflammatory cytokines and chemotactic factors that drive infiltration of immune cells into pancreatic islets [106]. Elevated levels of glucose induce expression of TXNIP leading to an enhanced production of IL-1β in pancreatic islets [100] as well as human and mouse adipose tissue [107], but not in macrophages [100]. The role of the NLRP3 inflammasome in β-cell dysfunction is illustrated in Fig. 4.

Bottom Line: We have reported mutations in NLRP3 that were found to be associated with certain diseases.In addition, we have reviewed the functional link between NLRP3 inflammasome, the regulator of cellular redox status Trx/TXNIP complex, endoplasmic reticulum stress and the pathogenesis of diseases such as type 2 diabetes.Finally, we have provided data on NLRP3 inflammasome, as a critical regulator involved in the pathogenesis of obesity and cardiovascular diseases.

View Article: PubMed Central - PubMed

Affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR 8256, Biological Adaptation and Ageing - IBPS, F-75005 Paris, France; CNRS-UMR 8256, F-75005 Paris, France; Inserm U1164, F-75005 Paris, France.

No MeSH data available.


Related in: MedlinePlus