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- | Journal: Hsp90 inhibition as a means to inhibit activation of the NLRP3 inflammasome. (Pubmed Central) - Oct 9, 2019
NLRP3 released from its protective complex became degraded by autophagy or secreted from the cells. Controlled destruction of NLRP3 is a potential way to regulate the inflammation associated with chronic diseases, such as AMD.
- | furosemide / generics
Preclinical, Journal: Comparison of iohexol and iodixanol induced nephrotoxicity, mitochondrial damage and mitophagy in a new contrast-induced acute kidney injury rat model. (Pubmed Central) - Oct 9, 2019
Our results showed that 48-h dehydration plus furosemide injection before iohexol administration successfully induced CI-AKI in rats...Plasma mtDNA may serve as a biological marker for renal mitochondrial disruption and damage in CI-AKI. Antioxidative defense and mitophagy are involved in the process of CI-AKI and may be promising targets of therapies.
- | Journal: Viral Strategies for Triggering and Manipulating Mitophagy. (Pubmed Central) - Oct 9, 2019
This enables viruses to promote persistent infection and attenuate the innate immune responses. In this review, we discuss the events of virus-regulated mitophagy and the functional relevance of mitophagy in the pathogenesis of viral infection and disease.
- | Journal: Chlamydia pneumoniae Hijacks a Host Autoregulatory IL-1β Loop to Drive Foam Cell Formation and Accelerate Atherosclerosis. (Pubmed Central) - Oct 9, 2019
Mature IL-1β and cholesterol may compete for access to the ABCA1 transporter to be exported from macrophages. C.pn exploits this metabolic-immune crosstalk, which can be modulated by NLRP3 inhibitors to alleviate atherosclerosis.
- | Journal: The Induction of IL-1β Secretion Through the NLRP3 Inflammasome During Ebola Virus Infection. (Pubmed Central) - Oct 8, 2019
This process is dependent on protease caspase-1, a component of the NLRP3 inflammasome complex, but is independent of virus replication. These findings may lead to the development of novel drugs that impede the pathogenesis of EBOV infection.
- | Journal: Toll-Like Receptor 4 and NLRP3 Caspase 1- Interleukin-1β-Axis are Not Involved in Colon Ascendens Stent Peritonitis-Associated Heart Disease. (Pubmed Central) - Oct 8, 2019
Despite developing cardiac dysfunction similar to wild types after CASP, Nlrp3 mice had reduced circulating levels of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α. Our results demonstrate that the genetic ablation of Tlr4, Nlrp3, and caspase-1 does not prevent the cardiac dysfunction, despite preventing the increase in pro-inflammatory cytokines, indicating that these are not feasible targets to therapy in high-grade sepsis.
- | Journal: NLRP3 inflammasome regulates Th17 differentiation in rheumatoid arthritis. (Pubmed Central) - Oct 8, 2019
These findings suggest a pathogenic role of NLRP3 inflammasome in RA by promoting Th17 cell differentiation. NLRP3 inflammasome could be a potential therapeutic target for the treatment of RA.
- | Clinical, Journal: NLRP3 Inflammasome-Related Proteins Are Upregulated in the Putamen of Patients With Multiple System Atrophy. (Pubmed Central) - Oct 8, 2019
We demonstrated that the density of microglia expressing NLRP3 inflammasome-related proteins was increased in the putamina of MSA cases and was significantly related to the deposition of phosphorylated α-synuclein-positive glial cytoplasmic inclusions, tyrosine hydroxylase-positive fiber loss, and gliosis of glial fibrillary acidic protein-positive astrocytes. Our study suggests that the NLRP3 inflammasome is significantly upregulated and correlates with the neurodegenerative process in MSA.
- | Journal: A Novel Derivative of the Natural Product Danshensu Suppresses Inflammatory Responses to Alleviate Caerulein-Induced Acute Pancreatitis. (Pubmed Central) - Oct 8, 2019
Interestingly, we found that the expression of nuclear factor-erythroid 2 related factor 2 (Nrf2) and its regulated antioxidant enzyme heme oxygenase-1 (HO-1), which modulate inflammatory activities, was significantly increased in DSC-treated groups. Together, our findings demonstrate that DSC alleviates pancreatic inflammation and damage in AP by inhibiting the activation of NF-κB, STAT3, and NLRP3 inflammasome and modulating immune cell responses.
- | Review, Journal: Betaine Inhibits Interleukin-1β Production and Release: Potential Mechanisms. (Pubmed Central) - Oct 8, 2019
For IL-1β release, betaine inhibits IL-1β release through blocking the exocytosis of IL-1β-containing secretory lysosomes, reducing the shedding of IL-1β-containing plasma membrane microvesicles, suppressing the exocytosis of IL-1β-containing exosomes, and attenuating the passive efflux of IL-1β across hyperpermeable plasma membrane during pyroptotic cell death, which are associated with ERK1/2/PLA and caspase-8/A-SMase signaling pathways. Collectively, this review highlights the anti-inflammatory property of betaine by inhibiting the production and release of IL-1β, and indicates the potential application of betaine supplementation as an adjuvant therapy in various inflammatory diseases associating with IL-1β secretion.
- | Journal: IL-9 Integrates the Host-Candida Cross-Talk in Vulvovaginal Candidiasis to Balance Inflammation and Tolerance. (Pubmed Central) - Oct 8, 2019
We further show that a timely IL-9 neutralization at the onset of the inflammatory response ameliorated symptoms and vaginal pathology. Given that vaginal fluids from patients with recurrent VVC had higher levels of IL-9, these findings, by providing novel insights into the pathogenesis of VVC, may pave the way for alternative therapeutic strategies based on IL-9 neutralization.
- | Journal: Leucine Rich Repeat Proteins: Sequences, Mutations, Structures, and Diseases. (Pubmed Central) - Oct 8, 2019
These mutations influence protein folding, aggregation, oligomerization, stability, protein-ligand interactions, disulfide bond formation, and glycosylation. Most of the mutations cause loss of function and a few, gain of function.
- | Preclinical, Journal: Ghrelin improves muscle function in dystrophin-deficient mdx mice by inhibiting NLRP3 inflammasome activation. (Pubmed Central) - Oct 8, 2019
Most of the mutations cause loss of function and a few, gain of function. Our findings reveal that ghrelin suppresses muscle inflammation and ameliorates disease phenotype through inhibition of NLRP3 inflammasome activation and the production of IL-1β in mdx mice, which suggests new therapeutic potential of ghrelin in DMD.
- | Journal: Role of NLRP3 inflammasome in the pathogenesis of alcoholic liver disease (Pubmed Central) - Oct 8, 2019
The NLRP3 inflammasome acts as a ligand-sensing element and plays an important role in mediating the immune and inflammatory response in the course of alcoholic liver disease. Thus, exploring the activation mechanism of NLRP3 inflammasome and its pathogenic role may provide a new idea in the clinical treatment of alcoholic liver disease.
- Ilaris (canakinumab) / Novartis
Cryopyrin-Associated Periodic Syndrome Treated with Canakinumab – Long-Term Follow-up Data Documents Sustained Safety and Remission (B218) - Oct 7, 2019 - Abstract #ACRARHP2019ACR_3975;
Thus, exploring the activation mechanism of NLRP3 inflammasome and its pathogenic role may provide a new idea in the clinical treatment of alcoholic liver disease. An interim analysis of the RELIANCE study, the longest running real-life CAN registry, shows that long-term CAN treatment is safe and effective in CAPS patients.
- dapansutrile (OLT-1177) / Olatec Industries
The First Phase 2a Proof-of-Concept Study of a Selective NLRP3 Inflammasome Inhibitor, Dapansutrile™ (OLT1177™), in Acute Gout (B206) - Oct 7, 2019 - Abstract #ACRARHP2019ACR_3892;
DapansutrileTM was shown to have a significant positive clinical anti-inflammatory effect and clean safety profile in the treatment of monoarticular gout attacks. The oral NLRP3 inhibitor showed a broad therapeutic range dosed at a daily 300-1000-2000mg and holds promise for further clinical development in acute gout.
- Asymptomatic Monosodium Urate Crystal Deposition Associates with Increased Expression of Pro-Inflammatory Genes (B206) - Oct 7, 2019 - Abstract #ACRARHP2019ACR_3891;
These results only reflect systemic responses on gene-expression, and cytokine assay is underway. Further studies are needed to validate these results in synovial fluid samples.
- Autoantibodies from Sjögren's Syndrome Enhance NLRP3 Inflammasome Activation and IL-18 Production in Human Salivary Gland Cell Line A-253 (Hall B5) - Oct 7, 2019 - Abstract #ACRARHP2019ACR_3491;
Endogenous RNA components of anti-SSA ICs and reactive oxygen species were responsible for this activation. Effect of NAC and RNase A digestion of supernatants on anti-SSA ICs induced IL-18 production in A-253 cells.
- Expanding the Phenotypic and Genotypic Spectrum in Yao Syndrome (Hall B5) - Oct 7, 2019 - Abstract #ACRARHP2019ACR_3120;
Recognition of the expanded disease spectrum will foster prompt diagnosis and management of the disease. Table 1final Table 1.
- Mononuclear Leukocyte DNA Methylome Imprinting of Networked Signaling and Immunity Regulatory Pathways in Gout (Hall B5) - Oct 7, 2019 - Abstract #ACRARHP2019ACR_3024;
Such changes, and differential TF-gene network DNA methylation in all PBMCs, were in contrast to lack of NLRP3 pathway imprinting. The PBMC DNA methylome signature likely helps determine phenotypic outcomes of not only acute gouty arthritis, but also granulomatous tophaceous and chronic inflammatory synovitis, and potentially modulates comorbidities in the disease.
- Multi-Organ System Meta-Analytic Approach to Investigating Sarcoidosis (Hall B5) - Oct 7, 2019 - Abstract #ACRARHP2019ACR_3022;
Our results emphasized the role of innate immune cell and Wnt activity in SD, among other signaling pathways, and suggest potential biomarkers and therapeutic targets. This approach to data analysis illustrates the importance of studying affected target organs to determine active pathways that are unique.
- Rituxan (rituximab) / Roche, Biogen
AGBL3 as a Novel Gene Associated with Hereditary Hypocomplementemic Urticarial Vasculitis and Favorable Response to Rituximab (Hall B5) - Oct 7, 2019 - Abstract #ACRARHP2019ACR_2177;
Potential pathogenic mechanisms and clinical picture are considered to be different from DNASE1L3 variants, which are also associated with monogenic lupus and defects in DNA clearance. Long term follow-up and search for other patients associated with AGBL3 variants among DNASE1L3-variant-negative hypocomplementemic urticarial vasculitis patients are required for better clarification of the AGBL3-associated clinical phenotype.
- Ilaris (canakinumab) / Novartis
A Retrospective Medical Chart Review of Patients with Periodic Fever Syndromes Initiating Canakinumab in the United States (Hall B5) - Oct 7, 2019 - Abstract #ACRARHP2019ACR_2165;
Figure 1. Reasons by PFS patients for discontinuation of treatments prior to canakinumab initiation Figure 2.
- Actemra IV (tocilizumab) / Roche, JW Pharma
Tocilizumab - An Effective Rescue Therapy for Refractory Unclassified Autoinflammatory Diseases in Children (Hall B5) - Oct 7, 2019 - Abstract #ACRARHP2019ACR_2155;
No unexpected adverse events occured. Clinical features and inflammatory markers rapidly improved; the response was sustained at the 12 months follow-up.
- Kineret (anakinra) / SOBI, Affibody
Anakinra Treatment in Recurrent Pericarditis: Single Center Experience (Hall B5) - Oct 7, 2019 - Abstract #ACRARHP2019ACR_2154;
Anakinra seems to be a safe and effective treatment approach for colchicine resistant recurrent pericarditis. However recurrence may occur during dose tapering.
- Monosodium Urate and Calcium Pyrophosphatecrystal-induced Interleukin 1 Production Depends on Glucose Uptake Through Glut1 Transporter (Hall B5) - Oct 7, 2019 - Abstract #ACRARHP2019ACR_2148;
Studies to decipher how these crystals induced Glut1 membrane localization are ongoing. Similarly, we investigate how glycolysis regulates NLRP3 and ASC activation.
- dapansutrile (OLT-1177) / Olatec Industries
Treatment with OLT1177™, an Oral NLRP3 Inflammasome Inhibitor, Reduces Systemic Inflammation During Gout Flares in Humans (Hall B5) - Oct 7, 2019 - Abstract #ACRARHP2019ACR_2147;
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Similarly, we investigate how glycolysis regulates NLRP3 and ASC activation. Oral OLT1177™, safe in humans, is a potential drug for the treatment of gout flares and other NLRP3 mediated diseases.
- Whole Blood RNA Sequencing Study of Gout Cases and Controls Demonstrates Transcriptomic Differences with Relevance to Inflammatory Cell Activation (Hall B5) - Oct 7, 2019 - Abstract #ACRARHP2019ACR_2142;
It is possible that this reflects true differences in the neutrophil gene expression program of gout-affected individuals compared to hyperuricemic and/or normouricemic controls. Reduced expression of TMEM176B has been shown to associate with activation of the NLRP3 inflammasome.
- Prevalence of Atopic Features in Classic Autoinflammatory Diseases (B207-B208) - Oct 7, 2019 - Abstract #ACRARHP2019ACR_1903;
However, both mild and severe eosinophilia are seen at a higher prevalence in CAPS, PAPA, and HA20, suggesting that NLRP3, PSTPIP1, and TNFAIP3mutations may alter eosinophil biology. Further studies are needed to determine the significance, disease associations, and treatment associations of eosinophilia in these diseases.
- Actemra IV (tocilizumab) / Roche, JW Pharma, Ilaris (canakinumab) / Novartis
Hepatitis a Virus Vaccination in Autoinflammatory Diseases Under Canakinumab and Tocilizumab Treatment (Hall B5) - Oct 7, 2019 - Abstract #ACRARHP2019ACR_1353;
The response to vaccine did not differ between healthy children and patients with autoinflammatory disease under canakinumab and tocilizumab. In this study hepatitis A vaccine was found to be safe in autoinflammatory diseases with canakinumab and tocilizumab treatment.
- Kineret (anakinra) / SOBI, Affibody
Preliminary Analysis of Hearing Loss in a Neonatal-Onset Multisystem Inflammatory Disease (NOMID) Cohort Followed over a Mean of 10 Years: Normal Hearing at Baseline and Early Treatment with Anakinra Area Associated with Maintenance of Normal Hearing (Hall B5) - Oct 7, 2019 - Abstract #ACRARHP2019ACR_1351;
Hearing loss, when present at baseline, typically progressed over time on treatment and was first detected with the HF-PTA. Persistent inner ear enhancement on FLAIR MRI was associated with progressive hearing and suggest the use of FLAIR MRI to monitor inner ear inflammation.
- Kineret (anakinra) / SOBI, Affibody
Cryopyrin-Associated Periodic Syndrome in Korea: 19 Years of Experience (Hall B5) - Oct 7, 2019 - Abstract #ACRARHP2019ACR_1350;
High index of suspicion and early intervention with anakinra is crucial to prevent potentially devastating outcomes. In addition this study suggest regular audiometry is necessary and hearing problem maybe the most sensitive factor to determine anakinra dose.
- Jakafi oral (ruxolitinib) / Novartis, Incyte, Orencia (abatacept) / BMS
Application of the Autoinflammatory Disease Activity Index (ADDI) to a Cohort of Patients in a Tertiary Hospital (Hall B5) - Oct 7, 2019 - Abstract #ACRARHP2019ACR_1349;
In our cohort the mean ADDI index was low and MSK has the highest score. GC intake was associated with a higher ADDI score.
- Kineret (anakinra) / SOBI, Affibody, Ilaris (canakinumab) / Novartis
Multiple Genetic Diagnoses in a Cohort of Patients with Cryopyrin Associated Periodic Syndrome (CAPS) (Hall B5) - Oct 7, 2019 - Abstract #ACRARHP2019ACR_1328;
Of 11 CAPS patients with pathogenic NLRP3 mutation, 4 had a secondary genetic diagnosis, which explained clinical features that were not attributable to CAPS. Our data suggest that further genetic testing should be considered to explain “phenotypic variability”.
- | Preclinical, Journal: Gamma-tocopherol ameliorates hyperglycemia-induced hepatic inflammation associated with NLRP3 inflammasome in alloxan-induced diabetic mice. (Pubmed Central) - Oct 5, 2019
The findings suggested that GT supplementation ameliorated hepatic damage by attenuating inflammation and oxidative stress in alloxan-induced diabetic mice. Taken together, GT could be a beneficial nutrient that can ameliorate inflammatory responses associated with NLRP3 inflammasome in hyperglycemia-induced hepatic damage.
- | Desoxyn (methamphetamine) / Lundbeck
Journal: Inflammasome Activation by Methamphetamine Potentiates Lipopolysaccharide Stimulation of IL-1β Production in Microglia. (Pubmed Central) - Oct 4, 2019
Blockade of capase-1 activity, lysosomal cathepsin B activity or mitochondrial ROS production by their specific inhibitors reversed the effects of Meth, demonstrating an involvement of inflammasome in Meth-induced microglia activation. Taken together, our results suggest that Meth triggers microglial inflammasome activation in a manner dependent on both mitochondrial and lysosomal danger-signaling pathways.
- | Journal: The NLRP3 Inflammasome Suppresses Protective Immunity to Gastrointestinal Helminth Infection. (Pubmed Central) - Oct 4, 2019
NLRP3-dependent suppression of immunity partially required CD4 cells but was apparent even in Rag1 mice that lack adaptive immune cells, suggesting that NLRP3 influences both innate and adaptive immunity. These data highlight a role for NLRP3 in limiting protective immunity to helminths, suggesting that targeting the NLRP3 inflammasome may be an approach for limiting the disease burden associated with helminth infections.
- | glibenclamide / generics
Preclinical, Journal: Glibenclamide protects against thioacetamide-induced hepatic damage in Wistar rat: investigation on NLRP3, MMP-2, and stellate cell activation. (Pubmed Central) - Oct 4, 2019
GLB treatment significantly downregulated the expressions of TGF-β1, α-SMA, NLRP3, ASC, caspase-1, and IL-1β, and upregulated MMP-2 and catalase against TAA-induced liver damage. The outcomes of the present study confirmed that GLB ameliorated the liver damage induced by TAA.
- | Flagyl (metronidazole) / SLA
Preclinical, Journal: Commensal bacteria aggravate allergic asthma via NLRP3/IL-1β signaling in post-weaning mice. (Pubmed Central) - Oct 4, 2019
Further study showed that metronidazole- and vancomycin-sensitive bacteria are involved in maintenance of NLRP3/IL-1β signal in pMφ. Our results suggest that certain species of commensal bacteria in post-weaning mice aggravate OVA-induced allergic asthma through NLRP3/IL-1β signal pathway.
- | Journal: Dynamics of Inflammatory Response in Autoinflammatory Disorders: Autonomous and Hyperinflammatory States. (Pubmed Central) - Oct 4, 2019
The dynamics of this latter group can be better defined as a "hyperinflammatory" state, which shares similar characteristics with the innate memory or trained immunity. Differentiation of "autonomous" and "hyperinflammatory" states of autoinflammatory disorders can provide additional insights to understand their pathogenesis and develop better management strategies since both conditions may have different inflammatory dynamics affecting the severity and frequency of clinical findings and treatment responses.
- | dexamethasone / generics
Journal: Anti-Inflammatory Effect of Cherry Extract Loaded in Polymeric Nanoparticles: Relevance of Particle Internalization in Endothelial Cells. (Pubmed Central) - Oct 3, 2019
In particular, the results demonstrate that natural CE protects endothelial cells from inflammatory stress when encapsulated in NPs based on quaternary ammonium chitosan. The CE beneficial effects were directly related with in vitro internalization of CE-loaded NPs.
- | Journal: NLRP3 inflammasome promotes diabetes-induced endothelial inflammation and atherosclerosis. (Pubmed Central) - Oct 3, 2019
Moreover, either high glucose or IL-1β promoted the expression of adhesion molecules, which were suppressed by NLRP3 knockdown or IL-1β receptor antagonist. These findings provide novel insights into pathological mechanisms of diabetic atherosclerosis and have potential therapeutic implications for cardiovascular complications in diabetes.
- | Tekturna (aliskiren) / PDL
Journal: Inhibition of IL-1β by Aliskiren Improved Renal AQP2 Expression and Urinary Concentration Defect in Ureteral Obstruction and Release. (Pubmed Central) - Oct 3, 2019
Moreover, the NF-κB inhibitor Bay 11-7082 blocked NLRP3 inflammasome activation and attenuated the decrease in AQP2 protein expression in primary cultured rat inner medullary collecting duct cells treated with angiotensin II. These results indicate that the renin inhibitor aliskiren increases water channel AQP2 expression at least partially by suppressing NLRP3 inflammasome activation in the obstructed kidneys of mice with BUO and BUO release.
- Myeloid-specific inflammasome signaling promotes tumor growth (Prince George's Exhibition Halls AB) - Oct 2, 2019 - Abstract #SITC2019SITC_956;
This work will have broad implications across all solid tumor types and will allow for the understanding of how myeloid-specific production of IL-1b promotes tumor growth. In addition, the proposed work will contribute to our basic knowledge of inflammasome activation within the tumor microenvironment.
- A Tumor PD-L1-NLRP3 Inflammasome Signaling Axis Drives Adaptive Resistance to Anti-PD-1 Immunotherapy (Prince George's Exhibition Halls AB) - Oct 2, 2019 - Abstract #SITC2019SITC_892;
The identification of the key PD-L1-STAT3-PKR-NLRP3 signaling axis responsible for this mechanism provides insight into promising strategies for augmenting the efficacy of checkpoint inhibitor immunotherapy as well as for monitoring the management of cancer patients undergoing these therapies. NLRP3 inhibitors represent promising agents for future anti-PD-1 combination clinical trials.
- | Journal: Mitochondria, the NLRP3 inflammasome and sirtuins in type 2 diabetes: new therapeutic targets. (Pubmed Central) - Oct 2, 2019
In this review article, we attempt to provide an overview of the existing literature concerning the crosstalk between mitochondrial impairment and the inflammasome, with particular attention to cellular and mitochondrial redox metabolism and the potential role of the NLRP3 inflammasome and sirtuins in the pathogenesis of type 2 diabetes. Additionally, we discuss potential targets for therapeutic intervention based on these molecular interactions.
- | Preclinical, Journal: Mesenchymal stromal cells inhibit NLRP3 inflammasome activation in a model of Coxsackievirus B3-induced inflammatory cardiomyopathy. (Pubmed Central) - Oct 2, 2019
The suppressive effect of MSC on inflammasome activation was associated with normalized expression of prominent regulators of myocardial contractility and fibrosis to levels comparable to control mice. In conclusion, MSC treatment in myocarditis could be a promising strategy limiting the adverse consequences of cardiac and systemic NLRP3 inflammasome activation.
- | Journal: New workflow for classification of genetic variants' pathogenicity applied to hereditary recurrent fevers by the International Study Group for Systemic Autoinflammatory Diseases (INSAID). (Pubmed Central) - Oct 2, 2019
The MOLGENIS software is available for reuse at http://github.com/molgenis/molgenis; the specific HRF configuration is available at http://molgenis.org/said/. The HRF pathogenicity classifications will be published on the INFEVERS database at https://fmf.igh.cnrs.fr/ISSAID/infevers/.
- | Journal: NLRP3 inflammasome is involved in the recognition of Paracoccidioides brasiliensis by Human Dendritic Cells and in the induction of Th17 cells. (Pubmed Central) - Oct 2, 2019
The HRF pathogenicity classifications will be published on the INFEVERS database at https://fmf.igh.cnrs.fr/ISSAID/infevers/. Altogether our data indicated that activation of NLRP3 presents an important role in both the induction of the initial inflammatory response and in the development of the acquired immune response associated with resistance to infection.
- | Journal: NLRP3 inflammasome mediates chronic intermittent hypoxia-induced renal injury implication of the microRNA-155/FOXO3a signaling pathway. (Pubmed Central) - Oct 2, 2019
Collectively, we demonstrated that miR-155 might be a positive-regulator of NLRP3 pathway by inhibiting the targeted FOXO3a gene. These results established a link between the miR-155/FOXO3a pathway and the NLRP3 inflammasome, suggesting pharmacological blockage of NLRP3 as a potential therapeutic strategy for OSA-associated chronic kidney disease.