NLRP3 Inflammasome Activation in Renal Injury: Long-Term Effectiveness and Safety of Blocking the IL-1 System in a Kidney Transplanted Patient Affected by AA Amyloidosis Secondary to Cryopyrin-Associated Periodic Syndromes (CAPS)

2021 ◽  
Vol 02 (03) ◽  
Author(s):  
Luigi Melfa ◽  
Chiara Rocca ◽  
Giorgia Comai ◽  
Gaetano LaManna ◽  
Roberto Scarpioni
Keyword(s):  
Nlrp3 Inflammasome ◽  
Renal Injury ◽  
Inflammasome Activation ◽  
Aa Amyloidosis ◽  
Nlrp3 Inflammasome Activation

scholarly journals Mitochondria-Targeted Antioxidant Mito-Tempo Protects Against Aldosterone-Induced Renal Injury In Vivo

2017 ◽  
Vol 44 (2) ◽  
pp. 741-750 ◽  
Author(s):  
Wei Ding ◽  
Tingyan Liu ◽  
Xiao Bi ◽  
Zhiling Zhang
Keyword(s):  
Electron Microscopy ◽  
Renal Function ◽  
Nlrp3 Inflammasome ◽  
Renal Injury ◽  
Periodic Acid ◽  
Inflammasome Activation ◽  
Periodic Acid Schiff ◽  
Nlrp3 Inflammasome Activation

Background/Aims: Growing evidence suggests mitochondrial dysfunction (MtD) and the Nlrp3 inflammasome play critical roles in chronic kidney disease (CKD) progression. We previously reported that Aldosterone (Aldo)-induced renal injury in vitro is directly caused by mitochondrial reactive oxygen species (mtROS)-mediated activation of the Nlrp3 inflammasome. Here we aimed to determine whether a mitochondria-targeted antioxidant (Mito-Tempo) could prevent Aldo-induced kidney damage in vivo. Methods: C57BL/6J mice were treated with Aldo and/or Mito-Tempo (or ethanol as a control) for 4 weeks. Renal injury was evaluated by Periodic Acid-Schiff reagent or Masson’s trichrome staining and electron microscopy. ROS were measured by DCFDA fluorescence and ELISA. MtD was determined by real-time PCR and electron microscopy. Activation of the Nlrp3 inflammasome and endoplasmic reticulum stress (ERS) was detected via western blot. Results: Compared with control mice, Aldo-infused mice showed impaired renal function, increased mtROS production and MtD, Nlrp3 inflammasome activation, and elevated ERS. We showed administration of Mito-Tempo significantly improved renal function and MtD, and reduced Nlrp3 inflammasome activation and ERS in vivo. Conclusion: Mitochondria-targeted antioxidants may attenuate Aldo-infused renal injury by inhibiting MtD, the Nlrp3 inflammasome, and ERS in vivo. Therefore, targeting mtROS might be an effective strategy for preventing CKD.

scholarly journals NLRP3 inflammasome activation contributes to long-term behavioral alterations in mice injected with lipopolysaccharide

Neuroscience ◽  
2017 ◽  
Vol 343 ◽  
pp. 77-84 ◽  
Author(s):  
Wei Zhu ◽  
Feng-Sheng Cao ◽  
Jun Feng ◽  
Hua-Weng Chen ◽  
Jie-Ru Wan ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Inflammasome Activation ◽  
Behavioral Alterations ◽  
Nlrp3 Inflammasome Activation

scholarly journals NLRP3-Inflammasome Inhibition during Respiratory Virus Infection Abrogates Lung Immunopathology and Long-Term Airway Disease Development

Viruses ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 692
Author(s):  
Carrie-Anne Malinczak ◽  
Charles F. Schuler ◽  
Angela J. Duran ◽  
Andrew J. Rasky ◽  
Mohamed M. Mire ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Severe Disease ◽  
Critical Role ◽  
Inflammasome Activation ◽  
Nlrp3 Inflammasome Activation ◽  
Increased Risk ◽  
Rsv Infection ◽  
Syncytial Virus

Respiratory syncytial virus (RSV) infects most infants by two years of age. It can cause severe disease leading to an increased risk of developing asthma later in life. Previously, our group has shown that RSV infection in mice and infants promotes IL-1β production. Here, we characterized the role of NLRP3-Inflammasome activation during RSV infection in adult mice and neonates. We observed that the inhibition of NLRP3 activation using the small molecule inhibitor, MCC950, or in genetically modified NLRP3 knockout (Nlrp3−/−) mice during in vivo RSV infection led to decreased lung immunopathology along with a reduced expression of the mucus-associated genes and reduced production of innate cytokines (IL-1β, IL-33 and CCL2) linked to severe RSV disease while leading to significant increases in IFN-β. NLRP3-inflammasome inhibition or deletion diminished Th2 cytokines and inflammatory cell infiltration into the lungs. Furthermore, NLRP3 inhibition or deletion during early-life RSV infection led to reducing viral-exacerbated allergic response in a mouse model of RSV-induced allergy exacerbation. Here, we demonstrated the critical role of NLRP3-inflammasome activation in RSV immunopathology and the related long-term airway alteration. Moreover, these findings suggest the NLRP3-inflammasome as a potential therapeutic target to attenuate severe RSV disease and limit childhood asthma development.

scholarly journals Platelet Inhibition Prevents NLRP3 Inflammasome Activation and Sepsis-Induced Kidney Injury

2021 ◽  
Vol 22 (19) ◽  
pp. 10330
Author(s):  
Marivee Borges-Rodriguez ◽  
Corbin A. Shields ◽  
Olivia K. Travis ◽  
Robert W. Tramel ◽  
Cedar H. Baik ◽  
...  
Keyword(s):  
Renal Function ◽  
Platelet Activation ◽  
Nlrp3 Inflammasome ◽  
Renal Injury ◽  
Cecal Ligation ◽  
Receptor Protein ◽  
Inflammasome Activation ◽  
Glomerular Injury ◽  
Activated Platelets ◽  
Nlrp3 Inflammasome Activation

Platelets, cellular mediators of thrombosis, are activated during sepsis and are increasingly recognized as mediators of the immune response. Platelet activation is significantly increased in sepsis patients compared to ICU control patients. Despite this correlation, the role of activated platelets in contributing to sepsis pathophysiology remains unclear. We previously demonstrated NOD-like receptor protein 3 inflammasome (NLRP3) inflammasome activation in sepsis-induced platelets from cecal-ligation puncture (CLP) rats. Activated platelets were associated with increased pulmonary edema and glomerular injury in CLP vs. SHAM controls. In this study, we investigated whether inhibition of platelet activation would attenuate NLRP3 activation and renal and pulmonary injury in response to CLP. CLP was performed in male and female Sprague Dawley (SD) rats (n = 10/group) to induce abdominal sepsis and SHAM rats served as controls. A subset of CLP animals was treated with Clopidogrel (10 mg/kg/day, CLP + CLOP) to inhibit platelet activation. At 72 h post-CLP, platelet activation and NLRP3 inflammasome assembly were evaluated, IL-1β and IL-18 were measured in plasma, and tissues, renal and pulmonary pathology, and renal function were assessed. Activated platelets were 7.8 ± 3.6% in Sham, 22 ± 6% in CLP and significantly decreased to 14.5 ± 0.6% in CLP + CLOP (n = 8–10/group, p < 0.05). NLRP3 inflammasome assembly was inhibited in platelets of CLP + CLOP animals vs. CLP. Significant increases in plasma and kidney IL-1β and IL-18 in response to CLP were decreased with Clopidogrel treatment. Renal injury, but not lung histology or renal function was improved in CLP + CLOP vs. CLP. These data provide evidence that activated platelets may contribute to sepsis-induced renal injury, possibly via NLRP3 activation in platelets. Platelets may be a therapeutic target to decrease renal injury in septic patients.

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