scholarly journals Implication of the NLRP3 Inflammasome in Bovine Age-Related Sarcopenia

2021 ◽  
Vol 22 (7) ◽  
pp. 3609
Author(s):  
Davide De Biase ◽  
Giuseppe Piegari ◽  
Francesco Prisco ◽  
Ilaria Cimmino ◽  
Ilaria d’Aquino ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Nlrp3 Inflammasome ◽  
Interleukin 1Β ◽  
Inflammasome Activation ◽  
Interleukin 18 ◽  
Necrosis Factor Alpha ◽  
Age Related ◽  
Factor Alpha ◽  
Bovine Skeletal Muscle ◽  
First Time

Sarcopenia is defined as the age-related loss of skeletal muscle mass, quality, and strength. The pathophysiological mechanisms underlying sarcopenia are still not completely understood. The aim of this work was to evaluate, for the first time, the expression of NLRP3 inflammasome in bovine skeletal muscle in order to investigate the hypothesis that inflammasome activation may trigger and sustain a pro-inflammatory environment leading to sarcopenia. Samples of skeletal muscle were collected from 60 cattle belonging to three age-based groups. Morphologic, immunohistochemical and molecular analysis were performed to assess the presence of age-related pathologic changes and chronic inflammation, the expression of NLRP3 inflammasome and to determine the levels of interleukin-1β, interleukin-18 and tumor necrosis factor alpha in muscle tissue. Our results revealed the presence of morphologic sarcopenia hallmark, chronic lymphocytic inflammation and a type II fibers-selective NLRP3 expression associated to a significant decreased number of immunolabeled-fibers in aged animals. Moreover, we found a statistically significant age-related increase of pro-inflammatory cytokines such as interleukin-1β and interleukin-18 suggesting the activation of NLRP3 inflammasome. Taken together, our data suggest that NLRP3 inflammasome components may be normally expressed in skeletal muscle, but its priming and activation during aging may contribute to enhance a pro-inflammatory environment altering normal muscular anabolism and metabolism.

scholarly journals Nutraceutical Strategies for Suppressing NLRP3 Inflammasome Activation: Pertinence to the Management of COVID-19 and Beyond

Nutrients ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 47
Author(s):  
Mark F. McCarty ◽  
Simon Bernard Iloki Assanga ◽  
Lidianys Lewis Luján ◽  
James H. O’Keefe ◽  
James J. DiNicolantonio
Keyword(s):  
Nlrp3 Inflammasome ◽  
Protein Complexes ◽  
Interleukin 1Β ◽  
Inflammasome Activation ◽  
Interleukin 18 ◽  
Medical Disorders ◽  
Nlrp3 Inflammasome Activation ◽  
Wide Range ◽  
Stress Signals ◽  
And Control

Inflammasomes are intracellular protein complexes that form in response to a variety of stress signals and that serve to catalyze the proteolytic conversion of pro-interleukin-1β and pro-interleukin-18 to active interleukin-1β and interleukin-18, central mediators of the inflammatory response; inflammasomes can also promote a type of cell death known as pyroptosis. The NLRP3 inflammasome has received the most study and plays an important pathogenic role in a vast range of pathologies associated with inflammation—including atherosclerosis, myocardial infarction, the complications of diabetes, neurological and autoimmune disorders, dry macular degeneration, gout, and the cytokine storm phase of COVID-19. A consideration of the molecular biology underlying inflammasome priming and activation enables the prediction that a range of nutraceuticals may have clinical potential for suppressing inflammasome activity—antioxidants including phycocyanobilin, phase 2 inducers, melatonin, and N-acetylcysteine, the AMPK activator berberine, glucosamine, zinc, and various nutraceuticals that support generation of hydrogen sulfide. Complex nutraceuticals or functional foods featuring a number of these agents may find utility in the prevention and control of a wide range of medical disorders.

scholarly journals Inhibiting NLRP3 inflammasome activation prevents copper-induced neuropathology in a murine model of Wilson’s disease

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jianjian Dong ◽  
Xun Wang ◽  
Chenchen Xu ◽  
Manli Gao ◽  
Shijing Wang ◽  
...  
Keyword(s):  
Murine Model ◽  
Nlrp3 Inflammasome ◽  
Wilson’S Disease ◽  
Wilson's Disease ◽  
Interleukin 1Β ◽  
Inflammasome Activation ◽  
Interleukin 18 ◽  
Caspase 1 ◽  
Nlrp3 Inflammasome Activation ◽  
The Brain

AbstractWilson’s disease (WD) is an inherited disorder characterized by excessive accumulation of copper in the body, particularly in the liver and brain. In the central nervous system (CNS), extracellular copper accumulation triggers pathological microglial activation and subsequent neurotoxicity. Growing evidence suggests that levels of inflammatory cytokines are elevated in the brain of murine WD models. However, the mechanisms associated with copper deposition to neuroinflammation have not been completely elucidated. In this study, we investigated how the activation of NLR family pyrin domain containing 3 (NLRP3) inflammasome contributes to copper-mediated neuroinflammation in an animal model of WD. Elevated levels of interleukin-1β, interleukin-18, interleukin-6, and tumor necrosis factor-α were observed in the sera of WD patients and toxic milk (TX) mice. The protein levels of inflammasome adaptor molecule apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC), cleaved caspase-1, and interleukin-1β were upregulated in the brain regions of the TX mice. The NLRP3 inflammasome was activated in the TX mice brains. Furthermore, the activation of NLRP3 inflammasome was noted in primary microglia treated with CuCl2, accompanied by the increased levels of cleaved caspase-1, ASC, and interleukin-1β. Blocking NLRP3 inflammasome activation with siNlrp3 or MCC950 reduced interleukin-1β and interleukin-18 production, thereby effectively mitigating cognitive decline, locomotor behavior impairment, and neurodegeneration in TX mice. Overall, our study demonstrates the contribution of copper overload-mediated activation of NLRP3 inflammasome to progressive neuropathology in the CNS of a murine model of WD. Therefore, blockade of the NLRP3 inflammasome activation could be a potential therapeutic strategy for WD.

Inhibition of NLRP3 inflammasome activation and pyroptosis with ethyl acetate fraction of Bungeanum ameliorated cognitive dysfunction in aged mice

2021 ◽  
Author(s):  
Meihuan Zhao ◽  
Yuan Dai ◽  
Ping Li ◽  
Jie wang ◽  
Tengyun Ma ◽  
...  
Keyword(s):  
Ethyl Acetate ◽  
Cognitive Dysfunction ◽  
Nlrp3 Inflammasome ◽  
Ethyl Acetate Fraction ◽  
Inflammasome Activation ◽  
Material Basis ◽  
Age Related ◽  
Nlrp3 Inflammasome Activation ◽  
Zanthoxylum Bungeanum ◽  
Zanthoxylum Bungeanum Maxim

Zanthoxylum bungeanum Maxim (Rutaceae), a homologous of medicine and foodstuff, has previously been demonstrated the potential prevention of age-related cognitive dysfunction. However, the mechanisms and material basis remain elusively understood....

scholarly journals Protective effect of exogenous hydrogen sulfide on diaphragm muscle fibrosis in streptozotocin-induced diabetic rats

2020 ◽  
Vol 245 (14) ◽  
pp. 1280-1289
Author(s):  
Rui Yang ◽  
Qiang Jia ◽  
Yan Li ◽  
Shomaila Mehmood
Keyword(s):  
Diabetes Mellitus ◽  
Skeletal Muscle ◽  
Hydrogen Sulfide ◽  
Nlrp3 Inflammasome ◽  
Respiratory Function ◽  
Diaphragm Muscle ◽  
Receptor Protein ◽  
Muscle Fibrosis ◽  
First Time ◽  
Oligomerization Domain

Diabetes mellitus has been shown to impair respiratory function. The diaphragm is an important skeletal muscle involved in respiration. Hydrogen sulfide (H2S) is one of the three endogenous gas messengers in mammals, which exhibits anti-fibrotic activity in some types of diabetes-related complications. However, whether and how H2S exerts its anti-fibrotic activity on the diabetic diaphragmatic muscle remains unclear. In this study, we explored the anti-fibrotic activity of exogenous H2S on the diaphragm using a streptozotocin (STZ)-induced diabetic rat model. The results showed that diaphragmatic biomechanical parameters were decreased, whereas the levels of inflammatory cytokines, collagen, and nucleotide-binding oligomerization domain-like receptor protein (NLRP) 3 inflammasome-related protein expression were increased in diabetic diaphragms. This implies that diabetes causes fibrosis of the diaphragm muscle through activation of NLRP3 inflammasome. After supplementation with exogenous H2S, the diaphragmatic biomechanical and pathological alterations were ameliorated and activation of NLRP3 inflammasome was inhibited, followed by a decline in diaphragm muscle inflammation and fibrosis. These results demonstrate for the first time that exogenous H2S effectively attenuates STZ-induced diabetic diaphragm muscle fibrosis, and that the underlying mechanism may be associated with suppression of the NLRP3 inflammasome-mediated inflammatory reaction. Impact statement Diabetes mellitus is a group of chronic metabolic disorders, which causes serious damage to a variety of organs, such as the retina, heart, and skeletal muscle. The diaphragm is an important skeletal muscle involved in respiration in mammals. Fibrosis of the diaphragm muscle affects its contractility, which in turn impairs respiratory function. Accumulating evidence suggests that exogenous hydrogen sulfide (H2S) exhibits anti-fibrotic activity in diabetes mellitus, but whether and how H2S exerts this anti-fibrotic effect in the diabetic diaphragm remains unclear. The current work for the first time reveals that exogenous H2S attenuates hyperglycemia-induced fibrosis of the diaphragm muscle and strengthens diaphragmatic biomechanical properties in diabetes mellitus, and the mechanism may involve the alleviation of collagen deposition by suppression of the nucleotide-binding oligomerization domain-like receptor protein (NLRP) 3 inflammasome-mediated inflammatory reaction. Therefore, H2S supplementation could be used as an efficient targeted therapy against the NLRP3 inflammasome in the diabetic diaphragm.

scholarly journals The Treponema denticola Surface Protease Dentilisin Degrades Interleukin-1β (IL-1β), IL-6, and Tumor Necrosis Factor Alpha

2006 ◽  
Vol 74 (4) ◽  
pp. 2462-2467 ◽  
Author(s):  
Meguru Miyamoto ◽  
Kazuyuki Ishihara ◽  
Katsuji Okuda
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis Factor Alpha ◽  
Tumor Necrosis ◽  
Mononuclear Cells ◽  
Interleukin 1Β ◽  
Treponema Denticola ◽  
Peripheral Blood Mononuclear ◽  
Necrosis Factor Alpha ◽  
Factor Alpha ◽  
Necrosis Factor

ABSTRACT Dentilisin is a major surface protease and virulence factor of the bacterium Treponema denticola. In this study, we found that T. denticola reduced inflammatory cytokines, including interleukin-1β (IL-1β), IL-6, and tumor necrosis factor alpha, in peripheral blood mononuclear cells through degradation by dentilisin.

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