- |||||||||| Journal: Early BBB breakdown and subacute inflammasome activation and pyroptosis as a result of cerebral venous thrombosis. (Pubmed Central) - Oct 2, 2019
These results show an inflammation driven pathophysiology of CVT that follows MMP9-mediated BBB breakdown, and identified several targets that can be targeted by pharmaceutical agents to improve the neuroinflammation that follows CVT, such as MMP9, NLRP3, and IL-1β. Some of these pharmaceutical agents are already in clinical practice or under clinical trials indicating a good potential for translating this work into patient care.
- |||||||||| Journal: Zika virus elicits inflammation to evade antiviral response by cleaving cGAS via NS1-caspase-1 axis. (Pubmed Central) - Oct 2, 2019
The enhanced stabilization of caspase-1 by NS1 promotes the cleavage of cGAS, which recognizes mitochondrial DNA release and initiates type I IFN signaling during ZIKV infection. NLRP3 deficiency increases type I IFN production and strengthens host resistance to ZIKVin vitro and in vivo Taken together, our work unravels a novel antagonistic mechanism employed by ZIKV to suppress host immune response by manipulating the interplay between inflammasome and type I IFN signaling, which might guide the rational design of therapeutics in the future.
- |||||||||| Clinical, Journal: A Case of Muckle-Wells Syndrome due to novel NLRP3 mutation. (Pubmed Central) - Oct 2, 2019
NLRP3 deficiency increases type I IFN production and strengthens host resistance to ZIKVin vitro and in vivo Taken together, our work unravels a novel antagonistic mechanism employed by ZIKV to suppress host immune response by manipulating the interplay between inflammasome and type I IFN signaling, which might guide the rational design of therapeutics in the future. No abstract available
- |||||||||| Review, Journal: Inflammasomes in Tissue Damages and Immune Disorders After Trauma. (Pubmed Central) - Oct 2, 2019
Characterizing the involvement of inflammasomes in the pathogenesis of post-trauma syndrome is a key issue as they may be potential therapeutic targets. This review summarizes the current knowledge on the roles of inflammasomes in trauma.
- |||||||||| Importance of the inflammasome and immunological changes in MDS (Hall A1) - Sep 30, 2019 - Abstract #DGHO2019DGHO_449;
Recent investigations have shown that activation of the NLRP3 inflammasome complex has more broad reaching importance, particularly as a possible disease-specific biomarker for MDS, and mechanistically, as a driver of cardiovascular morbidity/mortality in individuals with age-related, clonal hematopoiesis. Recognition of the mechanistic role of aberrant innate immune activation in MDS provides a new perspective for therapeutic development that could usher in a novel class of disease modifying agents.
- |||||||||| Journal: Enhanced Cardiomyocyte NLRP3 Inflammasome Signaling Promotes Atrial Fibrillation. (Pubmed Central) - Sep 30, 2019
Further investigations into the therapeutic efficacy and protocols are needed to confirm whether MCC950 treatment could be a promising candidate for clinical trials. Conclusions-Our study establishes a novel pathophysiological role for CM NLRP3-inflammasome signaling with a mechanistic link to the pathogenesis of AF, and establishes inhibition of NLRP3 as a potential novel AF-therapy approach.
- |||||||||| methylprednisolone / generics
COMPLEMENT C5/C5a ARE DRUGGABLE TARGETS AND ATTENUATE DUCT ATRESIA AND LIVER INFLAMMATION IN EXPERIMENTAL BILIARY ATRESIA (Sheraton Boston Hotel, Grand Ballroom) - Sep 29, 2019 - Abstract #AASLD2019AASLD_2632;
Experimental BA was induced in newborn mice by intraperitoneal (I.P.) injection of 1.0x106 ffu rhesus rotavirus (RRV) and injected daily either with normal saline (disease control) or 4 mg/kg methylprednisolone (steroid control)... Blocking complement components represents a novel approach to limit acute biliary pathogenesis in BA by regulating both cellular and molecular effectors of liver inflammation and injury.
- |||||||||| SPATIOTEMPORAL CONTROL OF NLRP3 INFLAMMASOME ASSEMBLY AND ACTIVATION BY GSK3β-PI4k2α AXIS (Hynes Convention Center, Ballroom BC) - Sep 29, 2019 - Abstract #AASLD2019AASLD_977;
Our novel findings suggest that increased circulating ASC protein and liver ASC aggregates could be responsible for progression of AH and could serve as AH biomarkers. Our results identify a critical role of metabolism-sensing GSK3b-PI4k2a axis in mediating NLRP3 activation, thus defining a new target for eliminating inflammation associated liver diseases.
- |||||||||| THE ROLE OF THE INFLAMMASOME IN CHOLESTATIC LIVER INJURY IN HUMANS AND MICE (Hynes Convention Center, Poster Hall - Hall B) - Sep 29, 2019 - Abstract #AASLD2019AASLD_772;
2) The source of this activity is likely mediated by macrophages but not hepatocytes. 3) Loss of inflammasome activity in the macrophages promotes anti-inflammatory M2 phenotype and paradoxically stimulates hepatic fibrosis.
- |||||||||| Kineret (anakinra) / SOBI, Affibody
Preclinical, Journal: NLRP3/IL-1β mediates denervation during bladder outlet obstruction in rats. (Pubmed Central) - Sep 28, 2019
Taken together these observations indicate that H-Ferritin acts as a DAMP following chronic liver injury that signals through ICAM-1 on hepatic stellate cells to mediate an inflammatory response mediated by endosomal- and inflammasome-mediated pathways. The NLRP3/IL-1β-mediated inflammation pathway plays a significant role in denervation during BOO.
- |||||||||| Ilaris (canakinumab) / Novartis
Journal: Cholesterol Efflux Pathways Suppress Inflammasome Activation, NETosis and Atherogenesis. (Pubmed Central) - Sep 28, 2019
The CANTOS trial (Canakinumab Antiinflammatory Thrombosis Outcome Study) showed that antagonism of interleukin (IL)-1β reduces coronary heart disease in patients with a previous myocardial infarction and evidence of systemic inflammation, indicating that pathways required for IL-1β secretion increase cardiovascular risk...Tangier Disease patients, who carry loss-of-function mutations inand have increased myeloid cholesterol content, showed a marked increase in plasma IL-1β and IL-18 levels.-Cholesterol accumulation in myeloid cells activates the NLRP3 inflammasome, which enhances neutrophil accumulation and NETosis in atherosclerotic plaques. Tangier Disease patients, who have increased myeloid cholesterol content, showed markers of inflammasome activation, suggesting human relevance.
- |||||||||| Review, Journal: Regulation of NLRP3 Inflammasome by Phosphorylation. (Pubmed Central) - Sep 28, 2019
Several kinases and phosphatases have been shown to control NLRP3 inflammasome activation in response to either exogenous pathogen infections or endogenous molecules, such as bile acids. In this review, we summarize our current knowledge of phosphorylation patterns and their functional role in the regulation of NLRP3 inflammasome, and suggest interesting areas for future research.
- |||||||||| Review, Journal: The Role of NLRP3 and IL-1β in the Pathogenesis of Inflammatory Bowel Disease. (Pubmed Central) - Sep 28, 2019
However, while both studies of murine models of gut disease and patients provide data that the main cytokine product generated by this inflammasome, IL-1β, does in fact contribute to inflammation in IBD, there is no evidence that IL-1β plays a decisive or prominent role in "ordinary" patients with IBD (Crohn's disease). On the other hand, there are several definable point mutations that result in over-active NLRP3 inflammasome activity and in these cases, the gut inflammation is driven by IL-1β and is treatable by biologic agents that block the effects of this cytokine.
- |||||||||| Journal: EK7 Regulates NLRP3 Inflammasome Activation and Neuroinflammation Post-traumatic Brain Injury. (Pubmed Central) - Sep 27, 2019
Collectively, the data demonstrated that NEK7, as a modulator, regulates NLRP3 inflammasomes and downstream neuroinflammation in response to K efflux, through NEK7-NLRP3 assembly, pro-caspase-1 recruitment, caspase-1 activation, and pyroptosis in nerve injuries, post-TBI. NEK7 may be a potential therapeutic target for attenuating neuroinflammation and nerve injury post-TBI.
- |||||||||| Journal: Calcium-sensing receptor activates the NLRP3 inflammasome in LS14 preadipocytes mediated by ERK1/2 signaling. (Pubmed Central) - Sep 26, 2019
We assessed NLRP3 inflammasome priming and assembly after cinacalcet-induced CaSR activation and evaluated if this activation is mediated by downstream ERK1/2 signaling in LS14 preadipocytes...We propose CaSR-dependent NLRP3 inflammasome activation in preadipocytes through ERK signaling as a novel mechanism for the development of adipose dysfunction, that may favor the cardiovascular and metabolic consequences of obesity. To the best of our knowledge, this is the first report linking the inflammatory effect of CaSR to NLRP3 inflammasome induction in adipose cells.
- |||||||||| Review, Journal: Targeting TLRs and the Inflammasome in systemic sclerosis. (Pubmed Central) - Sep 26, 2019
Although still widely debated, significant evidence points to upregulation of the innate immune response via the activity of Toll-like receptors (TLRs) and the NLRP3 inflammasome as the start points in a cascade of signaling events which drives excessive extracellular matrix protein production, causing fibrosis. Herein the recent breakthroughs which have implicated TLR signaling and the NLRP3 inflammasome in SSc and the novel therapeutic possibilities this introduces to the field will be discussed.
- |||||||||| Journal: Acute adrenal cortex injury during cardiopulmonary bypass in a canine model. (Pubmed Central) - Sep 22, 2019
CPB induces significant systemic and local inflammation in the adrenal cortex and results in cytological architectural and ultrastructural alterations in adrenocorticocytes. In addition, the NLRP3 inflammasome pathway might promote adrenal gland injury during CPB and might represent a novel potential therapeutic target.
- |||||||||| Ilaris (canakinumab) / Novartis
Review, Journal: NLRP3 Inflammasome and the IL-1 Pathway in Atherosclerosis. (Pubmed Central) - Sep 22, 2019
This concept was recently proven by CANTOS (Canakinumab Anti-Inflammatory Thrombosis Outcomes Study), which demonstrated the therapeutic potential of the monoclonal IL (interleukin)-1β-neutralizing antibody canakinumab...Consequently, NLRP3 inflammasome activation contributes to the vascular inflammatory response driving atherosclerosis development and progression. Here, we review the mechanisms of NLRP3 inflammasome activation and proinflammatory IL-1 family cytokine production in the context of atherosclerosis and discuss treatment possibilities in light of the positive outcomes of the CANTOS trial.
- |||||||||| Journal: The Potential Therapeutic Role of miR-223 in Bovine Endometritis by Targeting the NLRP3 Inflammasome. (Pubmed Central) - Sep 22, 2019
Meanwhile, in vivo studies showed that inhibition of mir-223 resulted in an enhanced pathology of mice during LPS-induced endometritis, while overexpression of mir-223 attenuated the inflammatory conditions in the uterus. In summary, our study highlights that miR-223 serves both to constrain the level of NLRP3 activation and to act as a protective factor in the inflammatory response and thus provides a future novel therapeutic modality for active flares in cow endometritis and other inflammatory diseases.
- |||||||||| carvedilol / generics
Journal: Repositioning of the β-Blocker Carvedilol as a Novel Autophagy Inducer That Inhibits the NLRP3 Inflammasome. (Pubmed Central) - Sep 22, 2019
In the in vivo mouse model of NLRP3-associated peritonitis, oral administration of CVL reduced (1) peritoneal recruitment of neutrophils; (2) the levels of IL-1β, IL-18, active caspase-1, ASC, IL-6, TNF-α, MCP-1, and CXCL1 in the lavage fluids; and (3) the levels of NLRP3 and HO-1 in the peritoneal cells. Our results indicated that CVL is a novel autophagy inducer that inhibits the NLRP3 inflammasome and can be repositioned for ameliorating NLRP3-associated complications.
- |||||||||| Journal: Differential role of the NLRP3 inflammasome in infection and tumorigenesis. (Pubmed Central) - Sep 22, 2019
NLRP3 is also associated with a wide variety of infections and tumorigenesis that are closely correlated with chemotherapy response and prognosis. In this review, we explore the rapidly expanding body of research on the expression and functions of NLRP3 in infections and cancers and outline novel inhibitors targeting the NLRP3 inflammasome that could be developed as therapeutic alternatives to current anticancer treatment.
- |||||||||| Review, Journal: NLRP inflammasome as a key role player in the pathogenesis of environmental toxicants. (Pubmed Central) - Sep 22, 2019
These molecules have been shown to suppress the NLRP3 inflammasome mostly through the regulation of cellular redox status and the nuclear factor-κB (NF-κB) pathway, rendering them potential promising compounds to overcome ET-mediated organ damage. In the present review, we have made an effort to extensively review the ETs that exert their pathogenesis via the stimulation of inflammation, their precise mechanisms of action and the possible protective agents that could be potentially used to protect against such toxicants.
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