- |||||||||| 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.
- |||||||||| 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, 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: 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: 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.
- |||||||||| 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.
- |||||||||| dactinomycin / Generic mfg., azithromycin / Generic mfg., macrocyclic peptide / UCB, Merck (MSD)
Rhesus theta defensin-1: an antimicrobial peptide with immunomodulatory properties for the treatment of cystic fibrosis. (HALL F) - Apr 5, 2019 - Abstract #ECCMID2019ECCMID_3797; Background: Rhesus Theta Defensin-1 (RTD-1) is a macrocyclic peptide isolated from Rhesus macaque leukocytes with dual anti-microbial and anti-inflammatory properties...Gene transcript stability was assessed using Actinomycin-D...THP-1 cytokine data for IL-1β and TNFα reveal RTD-1 more potently inhibits their production by 2-fold and 4-fold respectively when compared to Azithromycin, a commonly prescribed macrolide for treatment of airway inflammation in CF patients. These data demonstrate the anti-inflammatory mechanism of action of RTD-1 is partially mediated in part by inhibition of inflammasome activity.
- |||||||||| Kolchin (colchicine) / Incepta
Clinical, Journal: State of care for patients with systemic autoinflammatory diseases - Results of a tertiary care survey. (Pubmed Central) - Apr 4, 2019 ...The diagnostic work-up included inflammatory markers and genetic testing, the first line treatment interleukin-1 (IL-1) blockers for CAPS and colchicine for FMF...The overall state of care for SAID patients was rated to be excellent or good by only 12% of departments, and to be poor or non-sufficient by 40% of departments. This study demonstrates a high need to improve the state of care and to harmonize diagnostic and treatment strategies for SAID patients.
- |||||||||| Review, Journal: Recent advances in inflammasome biology. (Pubmed Central) - Apr 3, 2019
Activation of this complex often involves the adaptor protein ASC and upstream sensors including NLRP1, NLRP3, NLRC4, AIM2, and pyrin, which are activated by different stimuli including infectious agents and changes in cell homeostasis. Here we discuss new regulatory mechanisms that have been identified for the canonical inflammasomes, the most recently identified NLRP9b inflammasome, and the new gasdermin family of proteins that mediate pyroptosis and other forms of regulated cell death.
- |||||||||| Preclinical, Journal, IO Biomarker: Anti-inflammatory effect of cinnamaldehyde and linalool from the leaf essential oil of Cinnamomum osmophloeum Kanehira in endotoxin-induced mice. (Pubmed Central) - Apr 3, 2019
In addition, cinnamaldehyde and linalool at the dose equivalent to their corresponding content in the tested dose of the leaf essential oil, which was 0.9Â mg/kg and 5.2Â mg/kg, respectively, showed similar or slightly less inhibitory activity for most of these inflammatory parameters compared with that of the leaf essential oil. Our data confirmed the potential use of leaf essential oil of Cinnamomum osmophloeum Kanehira as an anti-inflammatory natural product and provide evidence for cinnamaldehyde and linalool as two potent agents for prophylactic use in health problems associated with inflammations that being attributed to over-activated TLR4 and/or NLRP3 signaling pathways.
- |||||||||| Review, Journal: Ion homeostasis and ion channels in NLRP3 inflammasome activation and regulation. (Pubmed Central) - Apr 3, 2019
Here, we discuss how the complex interplay of ion fluxes contributes to canonical, non-canonical, and alternative NLRP3 activation pathways that induce IL-1β secretion from immune cells. Particular attention is given to the concrete evidence for the involvement of ion channels, which may present viable therapeutic targets for the modulation of NLRP3 inflammasome activation.
- |||||||||| probenecid / generics
Journal: Inflammasome Activation Induces Pyroptosis in the Retina Exposed to Ocular Hypertension Injury. (Pubmed Central) - Apr 2, 2019 ...The OHT-induced release of cytokines and RGC death were significantly decreased in the retinas of Casp1Casp4(11), Panx1 and in Wild-type (WT) mice treated with the Panx1 inhibitor probenecid...Furthermore, they indicate an active contribution of neuronal NLRP1/NLRP3 inflammasomes and the pro-pyroptotic gasdermin D pathway to pathophysiology of the OHT injury. These results support the feasibility of inflammasome modulation for neuroprotection in OHT-injured retinas.
- |||||||||| Journal: Deoxycholic acid disrupts the intestinal mucosal barrier and promotes intestinal tumorigenesis. (Pubmed Central) - Mar 30, 2019
Moreover, DCA significantly reduced the level of secretory immunoglobulin A (sIgA), and promoted the polarization of M2 macrophages in the intestine of Apcmin/+ mice. In conclusion, these data suggested that DCA induced intestinal low grade inflammation and disrupted the mucosal physical and functional barriers, aggravating intestinal tumorigenesis.
- |||||||||| allopurinol / generics
Journal: NLRP3 inflammasome inhibition ameliorates tubulointerstitial injury in the remnant kidney model. (Pubmed Central) - Mar 29, 2019 ...Allopurinol (ALLO) inhibits xanthine oxidase (XOD) activity, and, consequently, reduces the production of uric acid (UA) and reactive oxygen species (ROS), both of which can activate the NLRP3 pathway...ALLO reduced renal NLRP3 activation, without interfering with the NF-κB pathway. These observations indicate that the tubulointerstitial antiinflammatory and antifibrotic effects of ALLO in the Nx model involve inhibition of the NLRP3 pathway, and reinforce the view that ALLO can contribute to arrest or slow the progression of CKD.
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