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- | Journal: Evodiamine Augments NLRP3 Inflammasome Activation and Anti-bacterial Responses Through Inducing α-Tubulin Acetylation. (Pubmed Central) - Apr 12, 2019
Resveratrol treatment reversed evodiamine-induced increases of IL-1β and interferon-γ, and decreased bacterial clearance in mice. Collectively, our results indicated that evodiamine augmented the NLRP3 inflammasome activation through inducing α-tubulin acetylation, thereby conferring intensified innate immunity against bacterial infection.
- | Journal: Cutting Edge: Mitochondrial Assembly of the NLRP3 Inflammasome Complex Is Initiated at Priming. (Pubmed Central) - Apr 11, 2019
An NLRP3 activation signal is then required for the calcium-dependent association of the adaptor molecule ASC with NLRP3 on the mitochondrial surface, resulting in inflammasome complex assembly and activation. These findings demonstrate a novel lipid interaction for caspase-1 and identify a role for mitochondria as supramolecular organizing centers in the assembly and activation of the NLRP3 inflammasome.
- | Journal: Inflammasome-Independent Leukotriene BProduction Drives Crystalline Silica-Induced Sterile Inflammation. (Pubmed Central) - Apr 11, 2019
BI-78D3, a JNK inhibitor, abrogated CS-induced neutrophilic inflammation in vivo in an air pouch model. These results highlight an inflammasome-independent and JNK activation-dependent lipidosome pathway as a regulator of LTBsynthesis and CS-induced sterile inflammation.
- | Journal: Cutting Edge: Blockade of Inhibitor of Apoptosis Proteins Sensitizes Neutrophils to TNF- but Not Lipopolysaccharide-Mediated Cell Death and IL-1β Secretion. (Pubmed Central) - Apr 11, 2019
In this study, we demonstrate that murine neutrophils can signal via TNFR1-driven ripoptosome assembly to induce both cell death and IL-1β maturation. However, unlike macrophages, neutrophils suppress TLR4-dependent cell death and NLRP3 inflammasome activation during IAP inhibition via deficiencies in the CD14/TRIF arm of TLR4 signaling.
- | CRISPR-Cas9 gene editing therapeutic / CRISPR Therap
Journal: Activation of the NLRP3 Inflammasome Pathway by Uropathogenic Escherichia coli Is Virulence Factor-Dependent and Influences Colonization of Bladder Epithelial Cells. (Pubmed Central) - Apr 11, 2019
The reduced colonization of NLRP3-deficient cells was type-1 fimbriae dependent. In conclusion, we found that the NLRP3 inflammasome was important for type-1 fimbriae-dependent colonization of bladder epithelial cells and that both type-1 fimbriae and α-hemolysin can modulate the activity of the NLRP3 inflammasome.
- | Journal: HSP60 critically regulates endogenous IL-1β production in activated microglia by stimulating NLRP3 inflammasome pathway. (Pubmed Central) - Apr 11, 2019
In conclusion, we found that the NLRP3 inflammasome was important for type-1 fimbriae-dependent colonization of bladder epithelial cells and that both type-1 fimbriae and α-hemolysin can modulate the activity of the NLRP3 inflammasome. HSP60 mediates microglial IL-1β production by regulating NLRP3 inflammasome pathway and reduction of HSP60 leads to reduction of inflammation in JEV infection.
- | Journal: Role of receptor-interacting protein 1/receptor-interacting protein 3 in inflammation and necrosis following chronic constriction injury of the sciatic nerve. (Pubmed Central) - Apr 11, 2019
The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/.
- | Journal: Candidalysin Crucially Contributes to Nlrp3 Inflammasome Activation by Candida albicans Hyphae. (Pubmed Central) - Apr 11, 2019
The Nlrp3 inflammasome is a crucial component of the innate immune system that provokes release of the IL-1β cytokine from myeloid cells upon encountering C. albicans hyphae. Our study reveals the peptide candidalysin as one of the hypha-derived drivers of Nlrp3 inflammasome responses in primary macrophages and, thus, contributes to better understanding the fungal mechanisms that determine the pathogenicity of C. albicans.
- | Journal: Modulation of calcium signaling pathway by hepatitis C virus core protein stimulates NLRP3 inflammasome activation. (Pubmed Central) - Apr 11, 2019
NLRP3 inflammasome activation by the HCV core protein required calcium mobilization linked with phospholipase-C activation. Our findings reveal a molecular basis of hepatic inflammasome activation and IL-1β release triggered by HCV core protein.
- | Journal: Estradiol inhibits NLRP3 inflammasome in fibroblast-like synoviocytes activated by lipopolysaccharide and adenosine triphosphate. (Pubmed Central) - Apr 11, 2019
Our findings reveal a molecular basis of hepatic inflammasome activation and IL-1β release triggered by HCV core protein. These results suggested the increased LPS and ATP in joint-space may promote knee OA by NLRP3 inflammasome and E2 may exert a protective effect by inhibiting the activation of NLRP3 inflammasome in FLS.
- | Journal: Soluble uric acid increases PDZK1 and ABCG2 expression in human intestinal cell lines via the TLR4-NLRP3 inflammasome and PI3K/Akt signaling pathway. (Pubmed Central) - Apr 11, 2019
These results suggested the increased LPS and ATP in joint-space may promote knee OA by NLRP3 inflammasome and E2 may exert a protective effect by inhibiting the activation of NLRP3 inflammasome in FLS. These findings suggest that urate upregulates the expression of PDZK1 and ABCG2 for excretion in intestinal cells via activating the TLR4-NLRP3 inflammasome and PI3K/Akt signaling pathway.
- | Clinical, Review, Journal: Calcium-Containing Crystals and Osteoarthritis: an Unhealthy Alliance. (Pubmed Central) - Apr 11, 2019
BCP crystals have been demonstrated to induce key mitogenic and inflammatory pathways and contribute to cartilage degradation. Calcium-containing crystals induce key inflammatory pathways and may represent an attractive novel target in OA, a condition devoid of effective treatments.
- | Clinical, Journal: Change in the expression of the NLRP3 inflammasome signaling pathway in peripheral blood and its significance in children with Mycoplasma pneumoniae pneumonia (Pubmed Central) - Apr 11, 2019
Calcium-containing crystals induce key inflammatory pathways and may represent an attractive novel target in OA, a condition devoid of effective treatments. The NLRP3 inflammasome signaling pathway might be involved in the pathogenesis of MPP in children and is closely associated with the severity and course of the disease.
- | Journal: Hypoxic expression of NLRP3 and VEGF in cultured retinal pigment epithelial cells: contribution of P2Y receptor signaling. (Pubmed Central) - Apr 11, 2019
The data indicate that hypoxia induces priming and activation of the NLRP3 inflammasome in cultured RPE cells. The hypoxic NLRP3 and VEGF gene expression and the secretion of VEGF are in part mediated by P2Y receptor signaling.
- | Journal: RORγ Regulates the NLRP3 Inflammasome. (Pubmed Central) - Apr 11, 2019
Additionally, RORg inverse agonists reduced mortality in a LPS/D-galactosamine induced fulminant hepatitis mouse model.  These results illustrate a major role for RORgin regulation of innate immunity via modulation of NLRP3 inflammasome activity. Furthermore, these data suggest that inhibiting the NLRP3 inflammasome with RORginverse agonists may be an effective method to treat NLRP3 associated diseases.
- | low molecular weight dextran sulfate (ILB) / TikoMed
Preclinical, Journal, IO Biomarker: The protective role of phloretin against dextran sulfate sodium-induced ulcerative colitis in mice. (Pubmed Central) - Apr 11, 2019
coli) and Lactobacillus levels were also re-balanced after phloretin treatment. These results indicate that phloretin might be a new dietary strategy for the treatment of UC.
- | Review, Journal: Roles of ginsenosides in inflammasome activation. (Pubmed Central) - Apr 10, 2019
Given this body of evidence, the functional relationship between ginsenosides and inflammasome activation provides new insight into the understanding of the molecular mechanisms of ginsenoside-mediated antiinflammatory actions. This relationship also has applications regarding the development of antiinflammatory remedies by ginsenoside-mediated targeting of inflammasomes, which could be used to prevent and treat inflammatory diseases.
- | Journal: Treatment of lidocaine on subacute thyroiditis via restraining inflammatory factor expression and inhibiting pyroptosis pathway. (Pubmed Central) - Apr 10, 2019
This relationship also has applications regarding the development of antiinflammatory remedies by ginsenoside-mediated targeting of inflammasomes, which could be used to prevent and treat inflammatory diseases. Lidocaine can improve SAT through inhibiting expression of inflammatory factors and the pyroptosis pathway.
- | Journal: Activation of NLRP3 signaling accelerates skin wound healing. (Pubmed Central) - Apr 10, 2019
Scratch assay revealed that ATP accelerated wound closure in mouse embryonic fibroblasts from WT mice but not from NALP3-KO mice. In conclusion, the present study demonstrated that NALP3 pathway activation is involved in wound repair, and the topical use of ATP may be useful as an effective treatment for accelerating wound healing.
- | Preclinical, Journal: Activation of dopamine D1 receptor decreased NLRP3-mediated inflammation in intracerebral hemorrhage mice. (Pubmed Central) - Apr 10, 2019
In conclusion, the present study demonstrated that NALP3 pathway activation is involved in wound repair, and the topical use of ATP may be useful as an effective treatment for accelerating wound healing. DRD1 activation by A68930 improves neurological outcome through inhibition of NLRP3-mediated inflammation in ICH mice.
- | Journal, IO Biomarker: Hypercapnia induces IL-1β overproduction via activation of NLRP3 inflammasome: implication in cognitive impairment in hypoxemic adult rats. (Pubmed Central) - Apr 10, 2019
DRD1 activation by A68930 improves neurological outcome through inhibition of NLRP3-mediated inflammation in ICH mice. The present results suggest that hypercapnia-induced IL-1β overproduction via activating the NLRP3 inflammasome by hypoxia-activated microglia may augment neuroinflammation, increase neuronal cell death, and contribute to the pathogenesis of cognitive impairments.
- | Preclinical, Journal: Evidence for the activation of pyroptotic and apoptotic pathways in RPE cells associated with NLRP3 inflammasome in the rodent eye. (Pubmed Central) - Apr 10, 2019
Our data suggest that two cell death pathways, pyroptosis and apoptosis, were activated in RPE cells after exposure to prolonged inflammasome activation, induced by a drusen component, Aβ. The involvement of two distinct cell death pathways in RPE sheds light on the potential interplay between these pathways and provides insights on the future development of therapeutic strategies for AMD.
- | Solodyn (minocycline) / Bausch Health
Journal: Microglial activation mediates chronic mild stress-induced depressive- and anxiety-like behavior in adult rats. (Pubmed Central) - Apr 10, 2019
The involvement of two distinct cell death pathways in RPE sheds light on the potential interplay between these pathways and provides insights on the future development of therapeutic strategies for AMD. These results together indicate that microglial activation mediates the chronic mild stress-induced depressive- and anxiety-like behavior and hippocampal neuro-inflammation.
- | Journal: Role of microbiota-derived lipopolysaccharide in adipose tissue inflammation, adipocyte size and pyroptosis during obesity. (Pubmed Central) - Apr 10, 2019
This influences the amount of LPS that is translocated from the gut. In particular, the lipid content of a meal may correlate with the amount of LPS built in to chylomicrons.
- | Journal: miRNA-23a/CXCR4 regulates neuropathic pain via directly targeting TXNIP/NLRP3 inflammasome axis. (Pubmed Central) - Apr 10, 2019
miR-23a, by directly targeting CXCR4, regulates neuropathic pain via TXNIP/NLRP3 inflammasome axis in spinal glial cells. Epigenetic interventions against miR-23a, CXCR4, or TXNIP may potentially serve as novel therapeutic avenues in treating peripheral nerve injury-induced nociceptive hypersensitivity.
- | Preclinical, Journal: IRE1α inhibition decreased TXNIP/NLRP3 inflammasome activation through miR-17-5p after neonatal hypoxic-ischemic brain injury in rats. (Pubmed Central) - Apr 10, 2019
IRE1a-induced UPR pathway may contribute to inflammatory activation and brain injury following neonatal HI. IRE1a activation, through decay of miR-17-5p, elevated TXNIP expression to activate NLRP3 inflammasome and aggravated brain damage.
- | Journal: The bacterial pigment pyocyanin inhibits the NLRP3 inflammasome through intracellular reactive oxygen and nitrogen species. (Pubmed Central) - Apr 10, 2019
PCN-induced intracellular ROS/RNS inhibited the NLRP3 inflammasome posttranslationally, and hydrogen peroxide or peroxynitrite alone were sufficient to block its activation. We propose that cytosolic ROS/RNS inhibit the NLRP3 inflammasome and that PCN's anti-inflammatory activity may help P. aeruginosa evade immune recognition.
- | Kineret (anakinra) / SOBI, Affibody, Ilaris (canakinumab) / Novartis
Journal: Systemic autoinflammation with intractable epilepsy managed with interleukin-1 blockade. (Pubmed Central) - Apr 10, 2019
Together, these findings suggest that patients with epilepsy responsive to immune modulation may have distinct autoinflammatory features supporting IL-1 blockade. As such, IL-1 blockade may be highly efficacious adjunctive medication for certain refractory epilepsy syndromes.
- | Biomarker, Clinical, Journal: Systemic activation of NLRP3 inflammasome in patients with severe primary Sjögren's syndrome fueled by inflammagenic DNA accumulations. (Pubmed Central) - Apr 9, 2019
Our data reveal the occurrence of systemic NLRP3 inflammasome activation in severe SS, which is associated with widespread extranuclear accumulations of inflammagenic DNA and impaired DNA degradation. These findings can provide novel biomarkers and new therapeutic targets for the management of SS patients with adverse outcomes.
- | Preclinical, Journal: Central blockade of NLRP3 reduces blood pressure via regulating inflammation microenvironment and neurohormonal excitation in salt-induced prehypertensive rats. (Pubmed Central) - Apr 9, 2019
Salt-induced prehypertension is partly due to the role of NLRP3 in PVN. Blockade of brain NLRP3 attenuates prehypertensive response, possibly via downregulating the cascade reaction triggered by inflammation and restoring the balance of neurotransmitters.
- | Review, Journal: Gain of function mutation and inflammasome driven diseases in human and mouse models. (Pubmed Central) - Apr 9, 2019
Furthermore, novel inhibitors of inflammasome complex formation such as MCC950 and related compounds attenuate experimental and clinical disease. The discovery of new GOF mutants of inflammasomes leading to further insights in pathomechanisms and the development of novel inhibitors represent a great challenge.
- | Journal: Critical role of NLRP3-caspase-1 pathway in age-dependent isoflurane-induced microglial inflammatory response and cognitive impairment. (Pubmed Central) - Apr 9, 2019
The discovery of new GOF mutants of inflammasomes leading to further insights in pathomechanisms and the development of novel inhibitors represent a great challenge. NLRP3 priming status in aged mouse brain may be involved in isoflurane-induced hippocampal inflammation and cognitive impairment.
- | Journal, IO Biomarker: Serum amyloid A primes microglia for ATP-dependent interleukin-1β release. (Pubmed Central) - Apr 9, 2019
P2XR-triggered IL-1β maturation and export is thus likely to represent an important contributor to this cytokine pool. Given that SAA is detected in Alzheimer disease and multiple sclerosis brain, together with IL-1β-immunopositive microglia, these findings propose a link between P2XR, SAA, and IL-1β in CNS pathophysiology.
- | Journal: Role of complement C5a and histones in septic cardiomyopathy. (Pubmed Central) - Apr 9, 2019
Many of these events occur after in vivo or in vitro contact of CMs with histones. Together, these data emphasize the role of complement (C5a) and C5a receptors (C5aR1, C5aR2), as well as extracellular histones in events that lead to cardiac dysfunction of sepsis (septic cardiomyopathy).
- | Review, Journal: NLRP3 inflammasome activation in inflammaging. (Pubmed Central) - Apr 9, 2019
Here, we summarize the current knowledge of mechanisms that drive both of these processes and focus our discussion the emerging concept that a key innate immune pathway, the NLRP3 inflammasome, is centrally involved in the recognition of triggers that appear during physiological aging and during metabolic stress. We further discuss how these processes are involved in the pathogenesis of common age-related pathologies and highlight potential strategies by which the detrimental inflammatory responses could be pharmacologically addressed.
- | metformin / generics
Journal: Piperine ameliorated lupus nephritis by targeting AMPK-mediated activation of NLRP3 inflammasome. (Pubmed Central) - Apr 9, 2019
We further discuss how these processes are involved in the pathogenesis of common age-related pathologies and highlight potential strategies by which the detrimental inflammatory responses could be pharmacologically addressed. By targeting AMPK, piperine significantly suppressed the activation of NLRP3 inflammasome, inhibited the release of pro-inflammatory cytokines, blocked the pyroptosis of tubular epithelial cells, and thus suppressed the development of LN.
- | Journal: Purification and Characterization of a Novel Pentadecapeptide from Protein Hydrolysates of Cyclina sinensis and Its Immunomodulatory Effects on RAW264.7 Cells. (Pubmed Central) - Apr 9, 2019
Furthermore, the expression of inhibitor of nuclear factor κB-α (IκB-α) was down-regulated. These findings suggest that SCSP might stimulate macrophage activities by activating the NF-κB signaling pathway and can be used as a potential immunomodulatory agent in functional food or medicine.
- | Clinical, Journal: Chlamydia pneumoniae is present in the dental plaque of periodontitis patients and stimulates an inflammatory response in gingival epithelial cells. (Pubmed Central) - Apr 9, 2019
Additionally, C. pneumoniae could infect GECs, leading to inflammation caused by activation of NF-κB and the NLRP3 inflammasome. We propose that the presence of C. pneumoniae in subgingival dental plaque may contribute to periodontal disease and could be used as a potential risk indicator of perio-dontal disease.
- | Journal: Curcumin Suppresses IL-1β Secretion and Prevents Inflammation through Inhibition of the NLRP3 Inflammasome. (Pubmed Central) - Apr 7, 2019
Taken together, we identified curcumin as a common NLRP3 inflammasome activation inhibitor. Our findings reveal a mechanism through which curcumin represses inflammation and suggest the potential clinical use of curcumin in NLRP3-driven diseases.
- | low molecular weight dextran sulfate (ILB) / TikoMed
Preclinical, Journal: Ginsenoside Rd ameliorates colitis by inducing p62-driven mitophagy-mediated NLRP3 inflammasome inactivation in mice. (Pubmed Central) - Apr 7, 2019
Furthermore, upregulation of AMPK/ULK1 signaling pathway accounted for Rd-induced autophagy, which was also seen in vivo. In conclusion, our results demonstrated the function of Rd on the inhibition NLRP3 inflammasome and its potential application for the treatment of NLRP3-associated diseases.
- | low molecular weight dextran sulfate (ILB) / TikoMed
Journal: The protective and anti-inflammatory effects of a modified glucagon-like peptide-2 dimer in inflammatory bowel disease. (Pubmed Central) - Apr 7, 2019
Importantly, the ameliorative effect of GLP-2â‘¡ was related to anti-apoptosis effect in colon tissues. These findings demonstrated that GLP-2â‘¡ may offer a superior therapeutic benefit over [Gly]GLP-2 monomer for treatment of IBD.
- | low molecular weight dextran sulfate (ILB) / TikoMed, CH-223191 / Celgene
Journal: Cardamonin, a natural flavone, alleviates inflammatory bowel disease by the inhibition of NLRP3 inflammasome activation via an AhR/Nrf2/NQO1 pathway. (Pubmed Central) - Apr 7, 2019
Finally, CH223191 was shown to abolish amelioration of cardamonin on DSS- and TNBS-induced colitis, inhibition of NLRP3 inflammasome activation and up-regulation of Nrf2 and NQO1 levels in colons. Taken together, cardamonin ameliorated colitis in mice through the activation of AhR/Nrf2/NQO1 pathway and consequent inhibition of NLRP3 inflammasome activation.
- | Clinical, Journal: NLRP3/Caspase-1 inflammasome activation is decreased in alveolar macrophages in patients with lung cancer. (Pubmed Central) - Apr 7, 2019
AMs also exhibited an impaired TLR4/LPS pathway as shown by the reduced induction of IL-6 and TNF-α. Our results support the hypothesis of tumour induced immunosuppression in the lung microenvironment and may provide novel targets for cancer immunotherapy.
- | Journal: The role of cell-crystal reaction mediated inflammation in the formation of intrarenal calcium oxalate crystals (Pubmed Central) - Apr 7, 2019
Recent studies indicated that inflammation induced by cell-crystal reaction can cause renal cell damage, stimulate intracellular expression of NADPH oxidase, trigger the massive production of reactive oxygen species, activate nuclear factor-κB signaling pathway, release a large number of inflammatory factors, and cause inflammatory cascade effect of the kidney, thus promoting the accumulation, nucleation and growth of calcium salt crystals, eventually leading to the formation of intrarenal crystals and even stones. In this process, the regulatory factors and mechanisms involved include macrophages, NLRP3-high mobility group box-1 protein inflammation network, fetuin A, autophagy activation and other factors.
- | Journal: Chlorogenic acid methyl ester exerts strong anti-inflammatory effects via inhibiting the COX-2/NLRP3/NF-κB pathway. (Pubmed Central) - Apr 7, 2019
In addition, CME affected the RAW264.7 cell cycle and inhibited the protein expressions of COX-2 and NLRP3 and prevented the phosphorylation of NF-κB p65 in RAW264.7 cells treated with LPS. These observations not only validated the anti-inflammatory effects of CME, but also revealed the underlying molecular basis, which involves the down-regulation of the expression of inflammatory factors and blockade of the COX-2/NLRP3/NF-κB signaling pathway.
- | Journal: Macrophage functionality and homeostasis in response to oligoethyleneglycol-coated IONPs: impact of a dendritic architecture. (Pubmed Central) - Apr 7, 2019
Effect of the dendritic architecture of the surface coating was investigated in a kinetic experiment involving cell short-term exposure (30 min or 1h30) to the two dendronized IONPs. NP10COP@2PG2 disrupted cellular homeostasis (LDH release, IL-1β and IL-8 secretion) to a greater extend than NP10COP@2PG1, which makes this last IONP the best candidate as MRI contrast or theranostic agent.
- | Journal: NLRP3 regulates macrophage M2 polarization through up-regulation of IL-4 in asthma. (Pubmed Central) - Apr 5, 2019
Collectively, we demonstrated here that activation of NLRP3 was engaged in the promotion of asthma. NLRP3, but not the inflammasome adaptor ASC or caspase-1, promoted the polarization of M2 macrophages through up-regulating the expression of IL-4, thereby contributing to its regulation of asthma.
- | Journal: IL-1β activation in response to Staphylococcus aureus lung infection requires inflammasome-dependent and independent mechanisms. (Pubmed Central) - Apr 5, 2019
By inhibiting neutrophil elastase, we were able to decrease IL-1β levels by 39% in Nlrp3 infected mice when compared to WT mice. These results highlight the crucial role of both proteases in IL-1β processing, via inflammasome-dependent and -independent mechanisms.
- | Kolchin (colchicine) / Incepta
Preclinical, Journal: Effect of Electroacupuncture on Synovial M 1/M 2 Macrophage Polarization in Rats with Acute Gouty Arthritis (Pubmed Central) - Apr 5, 2019
These results highlight the crucial role of both proteases in IL-1β processing, via inflammasome-dependent and -independent mechanisms. EA intervention can up-regulate the expression of arginase-1 mRNA and p-AMPKα protein, and down-regulate the expression of NOS 2, IL-1 β and NLRP 3 mRNAs in synovial tissues in AGA rats, which may contribute to its anti-inflammatory effect by promoting conversion of macrophages from M 1 pro-inflammatory phenotype to M 2 anti-inflammatory phenotype.
- | Preclinical, Journal: Ameliorative effect of gossypin against acute lung injury in experimental sepsis model of rats. (Pubmed Central) - Apr 5, 2019
GOS administration, may represent a novel treatment for the prevention of lung damage occurred after sepsis induction. This effect of GOS might be related to its anti-inflammatory potential that result in decreased cytokine response and improved oxidative status.