- |||||||||| Analysis of Brain Microglia and Behavior After LPS-Induced Systemic Inflammation in Mice (Floridian Ballroom) - Oct 17, 2019 - Abstract #ACNP2019ACNP_708;
A greater understanding of how NLRP3 inflammasome activation is triggered may reveal new therapeutic targets for the treatment of inflammatory disease. Our data unequivocally demonstrates neuroinflammation after peripheral LPS treatment, setting up a model to reliably test neuroinflammatory targets under systemic inflammation.
- |||||||||| Persistent Post-Operative Cognitive Dysfunction in Aging: Mechanisms Explored (Floridian Ballroom) - Oct 17, 2019 - Abstract #ACNP2019ACNP_635;
Our data unequivocally demonstrates neuroinflammation after peripheral LPS treatment, setting up a model to reliably test neuroinflammatory targets under systemic inflammation. Together, these findings indicate that opioid treatment following surgery, in the already vulnerable aged population initiates an exaggerated inflammatory cascade that may trigger, possibly via TLR4 activation, synaptic plasticity dysfunction to cause very long-lasting memory deficits.
- |||||||||| Preclinical, Journal, IO Biomarker: Repeated Morphine Prolongs Postoperative Pain in Male Rats. (Pubmed Central) - Oct 16, 2019
These studies indicate the morphine can have a deleterious effect on postoperative pain. These studies further suggest that longitudinal studies could be performed to test whether opioids similarly prolong postoperative pain in the clinic.
- |||||||||| Journal: The mitochondrial protease HtrA2 restricts the NLRP3 and AIM2 inflammasomes. (Pubmed Central) - Oct 16, 2019
Mechanistically, we show that the HtrA2 protease activity regulates autophagy and controls the magnitude and duration of inflammasome signaling by preventing prolonged accumulation of the inflammasome adaptor ASC. Our findings identify HtrA2 as a non-redundant mitochondrial quality control effector that keeps NLRP3 and AIM2 inflammasomes in check.
- |||||||||| Journal: Elucidation of The Anti-Inflammatory Effect of Vanillin In Lps-Activated THP-1 Cells. (Pubmed Central) - Oct 15, 2019
On the basis of the result, vanillin could effectively attenuate LPS-induced inflammatory response in THP-1 cells and was a potent anti-inflammatory component natural in food and beverage. These findings might contribute to the overall understanding of the potential health benefits of vanillin for food application.
- |||||||||| doxycycline / Generic Mfg.
Inflammasome-Mediated Cell Death Plays a Key Role in APOL1 Risk Variant-Induced Kidney Disease (201, Walter E. Washington Convention Center) - Oct 14, 2019 - Abstract #KIDNEYWEEK2019KIDNEY_WEEK_5106;
To define the role of inflammasome-mediated cell death in vivo, we crossed G2 APOL1 transgenic mice (Nphs1rtTA-TRE APOL1) with caspase-1 (Casp1-/-) or NLRP3 (Nlrp3-/-) knockout mice and induced podocyte G2 APOL1 expression with a 21-day doxycycline diet...Our results raise the possibility that inflammasome inhibition could be a potential therapeutic approach for APOL1-associated kidney disease. Funding NIDDK Support
- |||||||||| Nuclear Factor of Activated T Cells 5 (NFAT5) Mediates Peritoneal Fibrosis via Modulation of Nod-Like Receptor-3 (NLRP3) Inflammasome (Exhibit Hall, Walter E. Washington Convention Center) - Oct 14, 2019 - Abstract #KIDNEYWEEK2019KIDNEY_WEEK_4649;
In NFAT5+/- mice, ad-TGFβ induced peritoneal fibrosis were ameliorated with a reduction in peritoneal thickness compared to wild-type NFAT5 +/+ mice Conclusion This data suggest NFAT5 plays a key role in peritoneal fibrosis via tonicity-independent mechanism by either an inhibition of E-cadherin transcription and activation of NLRP3 inflammasome. Modulation of NFAT5 and NLRP3 inflammasome in peritoneum could be a novel approach to protect peritoneal fibrosis in PD patients
- |||||||||| belnacasan (VX-765) / Vertex
Implication of Inflammasome Activation in the Progression of Peritoneal Fibrosis in Mice (Exhibit Hall, Walter E. Washington Convention Center) - Oct 14, 2019 - Abstract #KIDNEYWEEK2019KIDNEY_WEEK_4645;
VX-765 (100 mg/kg/day), an inhibitor of caspase-1 activity, was administered by gavage for 2 weeks...Conclusion Our results suggest that inflammasome activation plays a pivotal role in the development of peritoneal fibrosis in infiltrated macrophages. Thus, inflammasome activation in macrophages could be a new therapeutic target for chronic inflammation-induced peritoneal fibrosis.
- |||||||||| CD248 Modulates Unfolded Protein Response in Diabetic Nephropathy (Exhibit Hall, Walter E. Washington Convention Center) - Oct 14, 2019 - Abstract #KIDNEYWEEK2019KIDNEY_WEEK_3955;
Our findings identify pericyte-specific CD248 as a potential target for therapeutic interventions of DN. Funding Government Support - Non-U.S.
- |||||||||| Evrenzo (roxadustat) / Astellas, AstraZeneca, FibroGen
Effect of Hypoxia-Inducible Factor-1α Stabilizers on the Destruction of Tight Junctions in Uremic Intestinal Epithelial Cells (Exhibit Hall, Walter E. Washington Convention Center) - Oct 14, 2019 - Abstract #KIDNEYWEEK2019KIDNEY_WEEK_3775;
The mRNA and protein expression of NLRP3, caspase-1 and IL-1β of Caco2 cells transfected miR-223-mimic decreased but that increased for tight junction protein, while transfection of miR-223-inhibitor, we got opposite results. Conclusion HIF-1α stabilizer (FG-4592) increases the decrease of HIF-1α expression under the stimulation of uremic serum, and its improvement of the expression mechanism of tight junction protein may play a role in the down-regulation of NLRP3 inflammasome caused by the up-regulation of miR-223 expression, thus improving the intestinal barrier function, which needs further experimental verification
- |||||||||| Evrenzo (roxadustat) / Astellas, AstraZeneca, FibroGen
Improvement of the Effect of HIF-1α Stabilizer on the Destruction of Tight Junctions in Intestinal Epithelial Cells Induced by Homocysteine (Exhibit Hall, Walter E. Washington Convention Center) - Oct 14, 2019 - Abstract #KIDNEYWEEK2019KIDNEY_WEEK_3774;
Background Based on previous findings that homocysteine (Hcy) can increase the permeability of intestinal epithelial Caco2 cell and lead to decreased expression of tight junction molecules, the role of HIF-1α in intestinal barrier dysfunction caused by homocysteine and the mechanism of intervention of HIF-1α stabilizer (FG-4592) on these effects were explored...Conclusion miR-223 may be involved in the maintenance of intestinal epithelial barrier function in the experiment of using uremic serum to stimulate Caco2 cells. HIF-1α stabilizer can improve the Hcy-induced reduction expression of HIF-1α, ZO-1, claudin-1, Occludin, up-regulate the expression of miR-223 and down-regulate the expression of NLRP3, the mechanism may involve the mir-223/NLRP3 pathway.
- |||||||||| Protein-Bound Uremic Toxins Induce NLRP3 Inflammasome Activation in Proximal Tubule Cells (Exhibit Hall, Walter E. Washington Convention Center) - Oct 14, 2019 - Abstract #KIDNEYWEEK2019KIDNEY_WEEK_3760;
Conclusion PBUTs are able to induce NLRP3 inflammasome activation in proximal tubule cells via oxidative stress, suggesting their involvement in a local inflammatory response in kidney disease. Funding Government Support - Non-U.S.
- |||||||||| ApoL1-DNA Cross-Talk with Cytosolic DNA Sensing Pathways in Podocytes (Exhibit Hall, Walter E. Washington Convention Center) - Oct 14, 2019 - Abstract #KIDNEYWEEK2019KIDNEY_WEEK_3055;
Conclusion ApoL1 variants provide a feed-forward response to STING pathway mediated inflammasome activation through cross-talk with cytosolic DNA sensing pathway. Funding NIDDK Support
- |||||||||| metformin / generics
PGC-1α Inhibits the NLRP3 Inflammasome via Preserving Mitochondrial Viability to Protect Kidney Fibrosis (Exhibit Hall, Walter E. Washington Convention Center) - Oct 14, 2019 - Abstract #KIDNEYWEEK2019KIDNEY_WEEK_2564;
The NLRP3 inflammasome pathway, mitochondrial dynamic proteins and morphology, oxidative stress marker, and profibrotic markers were examined after the TECs were treated with TGF-β1 (5 ng/ml) alone, TGF-β1+PGC-1α plasmid DNA (1 ug), TGF-β1+siPGC-1α (50 nM), and TGF-β1+PGC-1α activators (Metformin, AICAR, and Resveratrol)...These changes were significantly improved by PGC-1α activators. Conclusion This study demonstrates that kidney injury is ameliorated by PGC-1α-induced inactivation of the NLRP3 inflammasome.
- |||||||||| Apolipoprotein C3 Induces Systemic Inflammation and Organ Damage in CKD by Alternative Inflammasome Activation via a Novel Pathway (Exhibit Hall, Walter E. Washington Convention Center) - Oct 14, 2019 - Abstract #KIDNEYWEEK2019KIDNEY_WEEK_2550;
Conclusion These data provide novel insights into the regulation of the NLRP3 inflammasome activation in general and the pathophysiological role of triglyceride-rich lipoproteins containing ApoC3 in the progression of CKD and in CKD-associated cardiovascular disease. Targeting ApoC3 has the potential to prevent kidney damage and to provide an anti-inflammatory treatment strategy in patients with CKD.
- |||||||||| Hypoxia Reduced Renal Injury and Inflammation in Rats with Chronic Nitric Oxide Inhibition (Exhibit Hall, Walter E. Washington Convention Center) - Oct 14, 2019 - Abstract #KIDNEYWEEK2019KIDNEY_WEEK_2546;
Conclusion Tissue HYP exerted a protective effect in NAME, suggesting that it may influence a common pathogenic mechanism, which may relate to downregulation of the NLRP3 inflammasome/Casp1/IL1β and NFκB/IL6 pathways, and to limitation of oxidative stress. FAPESP/CNPq.Mean±SE;*p<0.05 vs respect C, #p<0,05 vs NNORFundingGovernment Support - Non-U.S.
- |||||||||| hydroxychloroquine / Generic Mfg., Uloric (febuxostat) / Takeda, Ipsen, Menarini, hydroxychloroquine / VG Lifesciences
Lysosome: At the Crossroads Between Na+-K+-ATPase and NLRP3 in Hyperuricemia-Induced Renal Tubular Injury (Exhibit Hall, Walter E. Washington Convention Center) - Oct 14, 2019 - Abstract #KIDNEYWEEK2019KIDNEY_WEEK_1809;
In vivo, SPF SD rats were divided (n=4 in each group) into control, HUA group [oxonic acid (OA) 750 mg/kg/d gavage for 8 weeks]; HCQ group (HCQ, with OA 750mg/kg/d for 8 weeks and HCQ 25 mg/kg/d gavage since the 5th week and for 4 weeks); and febuxostat group (Feb, with OA 750mg/kg/d for 8 weeks and Feb 3 mg/kg/d gavage since the 5th week for 4 weeks)...Conclusion UA induces lysosomal damage to release lysosomal contents and activate NLRP3 inflammasome. Lysosomal function protection could alleviate NKA-NLRP3 signaling pathway and effectively improve mitochondrial function in vitro and in vivo, suggesting that lysosome function plays an important role in HUA-induced renal tubular epithelial cell injury.
- |||||||||| Inflammasome Activation in Primary Hyperoxaluria (Exhibit Hall, Walter E. Washington Convention Center) - Oct 14, 2019 - Abstract #KIDNEYWEEK2019KIDNEY_WEEK_1571;
The latter might suggest protective factors in type III or predisposing factors in types I and II. Funding Commercial Support
- |||||||||| A Uromodulin Mutation Resulting in Innate Immune System Activation (Exhibit Hall, Walter E. Washington Convention Center) - Oct 14, 2019 - Abstract #KIDNEYWEEK2019KIDNEY_WEEK_1558;
A mouse model demonstrates that mutant protein enters the interstitium and blood and activates the innate immune system resulting in fibrosis with aging but improved repair following acute injury. Funding Veterans Affairs Support
- |||||||||| Knockout of Interleukin-36 Receptor Ameliorates AKI-to-CKD Transition via Prevention of Fibrosis and Inflammasome (Exhibit Hall, Walter E. Washington Convention Center) - Oct 14, 2019 - Abstract #KIDNEYWEEK2019KIDNEY_WEEK_1270;
Conclusion Our results demonstrate that IL-36α is up-regulated in renal tissues in both mouse and human AKI to CKD transition, and that IL-36α stimulates collagen type IV, CTGF, and inflammasome in AKI to CKD transition models. Thus, IL-36α/IL-36R blockage could serve as a potential therapeutic target in AKI to CKD transition.
- |||||||||| Role of NLRP3 in Rhabdomyolysis-Induced AKI (Exhibit Hall, Walter E. Washington Convention Center) - Oct 14, 2019 - Abstract #KIDNEYWEEK2019KIDNEY_WEEK_1100;
NLRP3 could play the essential role in RIAKI and and be a candidate as a treatment target. Funding Private Foundation Support
- |||||||||| Preclinical, Journal: Inflammasome inhibition prevents α-synuclein pathology and dopaminergic neurodegeneration in mice. (Pubmed Central) - Oct 13, 2019
Furthermore, oral administration of MCC950 in multiple rodent PD models inhibited inflammasome activation and effectively mitigated motor deficits, nigrostriatal dopaminergic degeneration, and accumulation of α-synuclein aggregates. These findings suggest that microglial NLRP3 may be a sustained source of neuroinflammation that could drive progressive dopaminergic neuropathology and highlight NLRP3 as a potential target for disease-modifying treatments for PD.
- |||||||||| Review, Journal: Targeting NLRP3 Inflammasome Activation in Severe Asthma. (Pubmed Central) - Oct 9, 2019
Here, we provide an overview of the pathophysiology of SA, present molecular mechanisms underlying aberrant inflammatory responses in the airways, summarize recent studies pertinent to the biology and functions of NLRP3, and discuss the role of NLRP3 in the pathogenesis of asthma. Finally, we contemplate the potential of targeting NLRP3 as a novel therapeutic approach for the management of SA.
- |||||||||| Review, Journal: Pyroptosis in Liver Disease: New Insights into Disease Mechanisms. (Pubmed Central) - Oct 9, 2019
Specifically, we will focus on the role of pyroptosis in alcoholic and non-alcoholic fatty liver disease, as well as in liver failure. Finally, the therapeutic implications of pyroptosis in liver diseases will be discussed.
- |||||||||| Journal: IL-18 cleavage triggers cardiac inflammation and fibrosis upon β-adrenergic insult. (Pubmed Central) - Oct 9, 2019
Inflammasome-dependent activation of IL-18 within the myocardium upon acute β-AR over-activation triggers cytokine cascades, macrophage infiltration and pathological cardiac remodelling. Blocking IL-18 at the early stage of β-AR insult can successfully prevent inflammatory responses and cardiac injuries.
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