- |||||||||| Long Form of Thymic Stromal Lymphopoietin Aggravates Pyroptosis of Human Airway Epithelium on Virus-Induced Asthma Exacerbation (PENNSYLVANIA CONVENTION CENTER, Hall D-E (200 Level), Area B) - Mar 15, 2020 - Abstract #ATS2020ATS_7381;
lfTSLP aggravated the activation of NLRP3 inflammasome ,the cleavage of GSDMD and the release of mature IL-1β in HDM-sensitized epithelial cells induced by poly(I:C),thus promoting epithelium pyroptosis. Consistent with this observation, Mouse TSLP expression, the ortholog of human lfTSLP, was found to be critical for the dysfunction of bronchial epithelial barrier and airway inflammation in murine model of viral asthma exacerbation, which could be suppressed by administration of TSLP mAb or human short form of thymic stromal lymphopoietin(sfTSLP).
- |||||||||| bleomycin / Generic mfg., BMS, sildenafil / Generic mfg.
Targeting the NLRP3 Inflammasome as a Novel Approach to Treat Pulmonary Hypertension (PENNSYLVANIA CONVENTION CENTER, Hall D-E (200 Level), Area D) - Mar 15, 2020 - Abstract #ATS2020ATS_7207;
Interventions commenced at day 14 (SuHx) or 7 (BLM) and included: NLRP3 inflammasome inhibitor MCC950 (10mgkg/day [low] or 20mg/kg/day [high]; s.c.), current therapy sildenafil (SILD; 30mg/kg/day; p.o.) or combination therapy (MCC950 10mg/kg/day + SILD)...Further, initial evidence suggests that IL-18 receptor signalling may be vital for SuHx-induced increases in RVSP. This highlights a previously unrecognised therapeutic option whereby selective targeting of the NLRP3 inflammasome, or its downstream cytokine IL-18, may provide a novel adjunct to current pulmonary vasodilator therapy.
- |||||||||| Increased NLRP3 and AIM2 Activation in IPF Alveolar Macrophages Is Associated with mtROS (PENNSYLVANIA CONVENTION CENTER, Hall D-E (200 Level), Area A) - Mar 15, 2020 - Abstract #ATS2020ATS_5991;
In lung fibrosis, mitochondrial dysfunction is associated with increased NLRP3 and AIM2 activation. Multiple insults in the fibrotic lungs could activate the Inflammasome and through IL-1b release, which could be associated with disease progression or acute exacerbations.
- |||||||||| Modulation of NLRP3 Inflammasome Activity by Endo-Lysosomal Proteins (PENNSYLVANIA CONVENTION CENTER, Room 126 A-B (100 Level)) - Mar 15, 2020 - Abstract #ATS2020ATS_4654;
NLRP3 is a poly-ubiquitinated protein. Modulation of STAMBP abundance and activity impacts the ubiquitination of NLRP3 to decrease NLRP3 abundance and inflammasome activity.
- |||||||||| The NLRP3 Inflammasome in the Cystic Fibrosis Macrophage (PHILADELPHIA MARRIOTT DOWNTOWN, Grand Ballroom Salon H-J (Level 5)) - Mar 15, 2020 - Abstract #ATS2020ATS_2815;
The variant was associated with greater IL-6 production in response to lipopolysaccharide, suggesting the possibility of crosstalk between inflammasome and non-inflammasome-mediated pathways. Our finding identifies a subset of people with CF who could benefit most from host-directed therapeutics targeting inflammasome pathways.
- |||||||||| Gasdermin D: A New Biomarker for Critically Ill Patients (PENNSYLVANIA CONVENTION CENTER, Room 122 A-B (100 Level)) - Mar 15, 2020 - Abstract #ATS2020ATS_2737;
Furthermore, GSDMD correlates with other pyroptotic effector molecules, namely IL-18. These results suggest pyroptosis, through interaction with other cell death pathways, may play a critical role in the dysregulated immune response in sepsis.
- |||||||||| Importance of the Mitochondrial Permeability Transition Pore (MPTP) for Initiation of NLRP3 Inflammasome Activation During Influenza (PENNSYLVANIA CONVENTION CENTER, Room 115 A-B (100 Level)) - Mar 15, 2020 - Abstract #ATS2020ATS_2495;
Real time PCR, ELISA, and western blotting were used to examine changes in gene and protein expression, respectively.ResultsOur findings demonstrate that the MPTP is essential for NLRP3 inflammasome activation in response to influenza. Along with reduced inflammatory cytokine expression, mice with impaired MPTP had decreased expression of multiple anti-viral genes, impaired mROS production, dysregulated immune cell infiltration, and decreased viral clearance.ConclusionData from this study sheds light on the critical role of MPTP in NLRP3 inflammasome activation and activation of the innate immune response to influenza.
- |||||||||| Clinical, Journal: Optimized protocols for studying the NLRP3 inflammasome and assessment of potential targets of CP-453,773 in undifferentiated THP1 cells. (Pubmed Central) - Mar 15, 2020
In summary, undifferentiated THP1 cells are fully competent for activation of the NLRP3 inflammasome and production of IL-1β, without differentiation into macrophages, and we describe optimized KD and KO methodologies to manipulate gene expression in these cells. As an example of the utility of undifferentiated THP1 cells for investigations into the biology of the NLRP3 inflammasome, we have used this cell system to rule out ABCb7 and ABCb10 as potential targets of the NLRP3 inflammasome inhibitor CP-453,773.
- |||||||||| Review, Journal: P2X7 receptor mediates NLRP3 inflammasome activation in depression and diabetes. (Pubmed Central) - Mar 14, 2020
We provide insights into the P2X7-NLRP3-IL-1β pathway as an important pathological mechanism and novel therapeutic target in diabetes and depression. Given that the P2X7-NLRP3-IL-1β pathway may play an important role in diabetes confounded by comorbid depression, the possibility of intervention with baicalin is proposed.
- |||||||||| Journal: lincRNA-Cox2 regulates NLRP3 inflammasome and autophagy mediated neuroinflammation. (Pubmed Central) - Mar 14, 2020
Knockdown of lincRNA-Cox2 inhibited the inflammasome activation and prevented the lincRNA-Cox2-triggered caspase-1 activation, leading to decreased IL-1β secretion and weakened TIR-domain-containing adapter-inducing interferon-β (TRIF) cleavage, thereby enhancing TRIF-mediated autophagy. Elucidation of the link between lincRNA-Cox2 and the inflammasome-autophagy crosstalk in macrophage and microglia reveals a role for lncRNAs in activation of NLRP3 inflammasome and autophagy, and provides new opportunities for therapeutic intervention in neuroinflammation-dependent diseases.
- |||||||||| Journal: Classification criteria for autoinflammatory recurrent fevers. (Pubmed Central) - Mar 14, 2020
Elucidation of the link between lincRNA-Cox2 and the inflammasome-autophagy crosstalk in macrophage and microglia reveals a role for lncRNAs in activation of NLRP3 inflammasome and autophagy, and provides new opportunities for therapeutic intervention in neuroinflammation-dependent diseases. Eurofever proposes a novel set of validated classification criteria for HRF and PFAPA with high sensitivity and specificity.
- |||||||||| Review, Journal: Role of the NLRP3 Inflammasome in Preeclampsia. (Pubmed Central) - Mar 13, 2020
Many DAMPs (uric acid, palmitic acid, high-mobility group box 1, advanced glycation end products, extracellular vesicles, cell-free DNA, and free fatty acids) are increased and associated with pregnancy complications, especially PE. This review focuses on the role of the NLRP3 inflammasome in the pathophysiology of PE.
- |||||||||| Alu RNA exacerbates experimental choroidal neovascularization via an inflammasome-dependent pathway (Exhibit Hall: Posterboard# B0146) - Mar 9, 2020 - Abstract #ARVO2020ARVO_6207;
One of the most aggressive forms of this disease known as wet AMD can drive patients to severe loss of vision even with adequate treatment (intraocular injection of drugs). Our study revealed new molecules that might be involved in wet-AMD development and progression, which are fundamental to create new treatment options.
- |||||||||| Effects of Probiotic on the Development of Diabetic Retinopathy (Exhibit Hall: Posterboard# B0196) - Mar 9, 2020 - Abstract #ARVO2020ARVO_5734;
After the treatment the retinal health was analyzed via fundus imaging, fluorescence angiography, optical coherence tomography, and electroretinogram. Also, inflammatory mediators such as IL-1b, caspase-1, and NLRP3 were determined for the evidence of cell death via pyroptosis/inflammation.Results Body weights of Akita mice were significantly lowered, the blood glucose levels, and the intraocular pressure (IOP) were reduced as well in the mice treated mice in comparison to the control (untreated mice).Conclusions Prolonged daily administration of a probiotic had a significant health benefit effects on ocular health as it was able to reduce IOP, and the blood glucose levels in chronic disease models of type 1 diabetes.Gut microbiota health is important for ocular functions.
- |||||||||| Development of pegylated arginase 1 as a therapy for retinal ischemic injury (Ballroom III) - Mar 9, 2020 - Abstract #ARVO2020ARVO_4725;
The study identifies the cross talk between the enzymes of the arginase pathway and histone deacetylases in certain immune cells called myeloid cells that infiltrate the retina under pathological conditions. Moreover, it has the potential to translate the inverstigational drug, pegylated-arginase 1 as a new therapy for these retinal disorders.
- |||||||||| Mechanotransduction and Retrotransposons in Age-Related Macular Degeneration (Exhibit Hall: Posterboard# A0168) - Mar 9, 2020 - Abstract #ARVO2020ARVO_4345;
In the past decades, AMD research has been primarily focused on studying the biochemical components of these deposits and their effects on the RPE. This study suggests a paradigm shift in our understanding of the pathogenesis of GA by identifying how the mechanical effects of these sub-RPE deposits modulate RPE homeostasis by dysregulating Alu retrotransposon catabolism whose role in GA has been well established.
- |||||||||| Activation of keratocyte NLRP3 inflammasome in a model of endothelial keratopathy (Exhibit Hall: Posterboard# A0398) - Mar 9, 2020 - Abstract #ARVO2020ARVO_3544;
Upregulated expressions of Caspase-1 p10, NLRP3 proteins were noted in activated keratocytes vs controls.Conclusions Our study showed keratocytes activation with upregulated NLRP3 pathway in a rabbit model of endothelial keratopathy. Proinflammatory cytokines may contribute to keratocyte activation and fibrosis, which in turn influences corneal homeostasis via inflammatory pathway in endothelial keratopathy.
- |||||||||| InflaMab: A novel NLRP3 Inflammasome inhibitor provides neuroprotection in a mouse model of glaucoma (Ballroom II) - Mar 9, 2020 - Abstract #ARVO2020ARVO_2933;
Confocal microscopy revealed a significant reduction of caspase-1 activation in THP1 cells treated with InflaMab as opposed to non-treated cells. In vivo, a single intravitreal injection of Inflamab provided significant neuroprotection in terms of RGC function (pERG amplitude) and RGC and axon survival when compared to untreated controlsConclusions These data demonstrate that (i) InflaMab inhibits inflammasome activation and (ii) intravitreal administration of InflaMab provides sustained neuroprotection in an inducible mouse model of glaucoma.
- |||||||||| Commensal microbiota as possible pathobiont in autoinflammatory disease (Room 310) - Mar 9, 2020 - Abstract #ARVO2020ARVO_2880;
While mice appear to use γδ T cells to respond to the commensal C. mast with IL-17 production, in patients this role may be taken on by other cells, or other commensals may be the stimulus. If indeed the conjunctivitis in CAPS patients reflects a response to their own commensals, adjunct antimicrobial therapy may be considered.
- |||||||||| Arginase 2 deletion protected against retinopathy associated with western diet-induced obesity (Exhibit Hall: Posterboard# B0197) - Mar 9, 2020 - Abstract #ARVO2020ARVO_2190;
BREC exposed to PA+HG exhibited elevated levels of A2, inflammasome components, and Tunel+ cells (cell death). These effects were prevented or blunted by arginase inhibition (p<0.05).Conclusions This study showed that A2 is critically involved in western diet-induced retinal oxidative stress, inflammation, and exaggerated photoreceptor light response.
- |||||||||| C/EBPβ promotes NLRP3 transcription and the inflammatory response in Aβ1-40-mediated retinal pigment epithelium cell injury (Exhibit Hall: Posterboard# A0218) - Mar 9, 2020 - Abstract #ARVO2020ARVO_1966;
miR-191-5p, as a repressor of C/EBPβ, protected RPE cells from Aβ1-40-induced injury by inhibiting C/EBPβ.Conclusions This study clarifies that C/EBPβ is a new transcriptional regulator of NLRP3 and that miR-191-5p, as an inflammatory repressor, can protect RPE cells from Aβ1-40-mediated impairment. These findings are useful in understanding the regulatory mechanism of the NLRP3 inflammasome involved in Aβ1-40-induced RPE cell injury and shed light on novel preventive and therapeutic approaches for RPE injury.
- |||||||||| A small molecule inhibitor of interleukin-1 receptor prevents light-induced retinal degeneration by modulating subretinal inflammation (Exhibit Hall: Posterboard# A0251) - Mar 9, 2020 - Abstract #ARVO2020ARVO_1668;
The inhibition of the inflammatory response in vivo by 101.10 reduced caspase-3 immunoreactivity and the number of TUNEL-positive photoreceptors, and preserved retinal function in mice exposed to blue light.Conclusions 101.10 attenuates subretinal inflammation and preserves the integrity and function of photoreceptors in a light model of retinal degeneration. Modulation of the IL-1 receptor is a promising strategy for preserving photoreceptor integrity in ocular degenerative diseases.
- |||||||||| Inflammasome facilitates ganglion cell loss via pyroptosis and apoptosis in ocular hypertension injury (Exhibit Hall: Posterboard# A0098) - Mar 9, 2020 - Abstract #ARVO2020ARVO_1608;
The activation of inflammasome and gasdermin D was also detected in DBA2/J retinas following the onset of IOP elevation.Conclusions The endogenous neuronal and glial inflammasomes, triggered by OHT spikes as well initiation of chronic OHT in glaucoma, activate gasderminD membrane pore formation on cell and mitochondrial membranes in vulnerable RGCs. These results support our new model (Figure) that links retinal inflammasomes with RGC dysfunction and/or death via apoptosis and/or pyroptosis after spiking and chronic OHT injury, including glaucoma.
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