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https://www.readbyqxmd.com/read/28544564/podocyte-activation-of-nlrp3-inflammasomes-contributes-to-the-development-of-proteinuria-in-lupus-nephritis
#1
Rong Fu, Chaohuan Guo, Shuang Wang, Yuefang Huang, Ou Jin, Haoqiang Hu, Jingxian Chen, Bihua Xu, Mianjing Zhou, Jijun Zhao, Sun-Sang J Sung, Hongyang Wang, Felicia Gaskin, Niansheng Yang, Shu-Man Fu
Objective Development of proteinuria in lupus nephritis (LN) is associated with podocyte dysfunction. The NLRP3 inflammasome has been implicated in the pathogenesis of LN. This study investigates whether NLRP3 inflammasome activation is involved in the development of podocyte injury in LN. Methods A fluorescence-labeled caspase-1 inhibitor probe was used to detect the activation of NLRP3 inflammasomes in podocytes in lupus-prone NZM2328 mice and in renal biopsies from LN patients. MCC950, a selective inhibitor of NLRP3, was used to treat NZM2328 mice...
May 23, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28539262/synthetic-anti-endotoxin-peptides-inhibit-cytoplasmic-lps-mediated-responses
#2
Anja Pfalzgraff, Lena Heinbockel, Qi Su, Klaus Brandenburg, Günther Weindl
Toll-like receptor (TLR) 4-independent recognition of lipopolysaccharide (LPS) in the cytosol by inflammatory caspases leads to non-canonical inflammasome activation and induction of IL-1 secretion and pyroptosis. The discovery of this novel mechanism has potential implications for the development of effective drugs to treat sepsis since LPS-mediated hyperactivation of caspases is critically involved in endotoxic shock. Previously, we demonstrated that Pep19-2.5, a synthetic anti-endotoxin peptide, efficiently neutralises pathogenicity factors of Gram-negative and Gram-positive bacteria and protects against sepsis in vivo...
May 21, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28536183/the-nlrp3-inflammasome-contributes-to-sarcopenia-and-lower-muscle-glycolytic-potential-in-old-mice
#3
Marin Jane McBride, Kevin P Foley, Donna M D'souza, Yujin E Li, Trevor C Lau, Thomas J Hawke, Jonathan D Schertzer
The mechanisms underpinning decreased skeletal muscle strength and slowing of movement during aging are ill-defined. "Inflammaging" - increased inflammation with advancing age - may contribute to aspects of sarcopenia, but little is known about the participatory immune components. We discovered that aging was associated with increased caspase-1 activity in mouse skeletal muscle. We hypothesized that the caspase-1 containing NLRP3 inflammasome contributes to sarcopenia in mice. Male C57BL/6J wild type (WT) and NLRP3(-/-) mice were aged to 10 months (adult) and 24 months (old)...
May 23, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28535504/long-non-coding-rna-kcnq1ot1-promotes-cataractogenesis-via-mir-214-and-activation-of-the-caspase-1-pathway
#4
Xin Jin, Hao Jin, Yan Shi, Yiyuan Guo, Hong Zhang
BACKGROUND/AIMS: KCNQ1OT1 regulates the expression of tissue-specific imprinted genes within the Kcnq1 domain. Imprinted genes are positive regulators of apoptosis, one of the forms of cell death related to cataract formation, and thus may provide novel therapeutic targets for cataract treatment. Here, we studied the role of non-coding RNAs(ncRNA) in cataract formation. METHODS: Human lens epithelium cells (HLECs) were treated with H2O2, and the expression of KCNQ1OT1 and miR-214 was detected by qRT-PCR...
May 25, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28532818/tdp-43-upregulation-mediated-by-the-nlrp3-inflammasome-induces-cognitive-impairment-in-2-2-4-4-tetrabromodiphenyl-ether-bde-47-treated-mice
#5
Juan Zhuang, Xin Wen, Yan-Qiu Zhang, Qun Shan, Zi-Feng Zhang, Gui-Hong Zheng, Shao-Hua Fan, Meng-Qiu Li, Dong-Mei Wu, Bin Hu, Jun Lu, Yuan-Lin Zheng
It is now commonly known that exposure to polybrominated diphenyl ethers (PBDEs) may cause neurotoxicity and cognitive deficits in children as well as adults, but the underlying mechanisms are still not clear. In the present study, we aimed to elucidate the potential underlying mechanism of 2, 2', 4, 4'-tetrabromodiphenyl ether (BDE-47)-induced neurotoxicity and cognitive impairment. Our results showed that BDE-47-treated mice exhibited impaired cognition and robust upregulation of nuclear TDP-43 in the hippocampus...
May 19, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28531279/mechanisms-governing-inflammasome-activation-assembly-and-pyroptosis-induction
#6
Sannula Kesavardhana, Thirumala-Devi Kanneganti
Inflammasomes are multimeric protein complexes that regulate inflammatory responses and pyroptotic cell death to exert host defense against microbes. Intracellular pattern-recognition receptors such as nucleotide-binding domain and leucine-rich repeat receptors (NLRs) and absent in melanoma 2 like receptors (ALRs) assemble the inflammasome complexes in response to pathogens and danger or altered-self signals in the cell. Inflammasome sensors, in association with an adaptor protein - apoptosis associated speck-like protein containing a caspase-activation and -recruitment domain (ASC) - activate inflammatory caspase-1 to enable the release of inflammatory cytokines and induce cell death, conferring host defense against pathogens...
May 20, 2017: International Immunology
https://www.readbyqxmd.com/read/28526339/magnesium-isoglycyrrhizinate-blocks-fructose-induced-hepatic-nf-%C3%AE%C2%BAb-nlrp3-inflammasome-activation-and-lipid-metabolism-disorder
#7
Xiao-Juan Zhao, Yan-Zi Yang, Yan-Jing Zheng, Shan-Chun Wang, Hong-Mei Gu, Ying Pan, Shui-Juan Wang, Hong-Jiang Xu, Ling-Dong Kong
Magnesium isoglycyrrhizinate as a hepatoprotective agent possesses immune modulation and anti-inflammation, and treats liver diseases. But its effects on immunological-inflammatory and metabolic profiles for metabolic syndrome with liver injury and underlying potential mechanisms are not fully understood. In this study, magnesium isoglycyrrhizinate alleviated liver inflammation and lipid accumulation in fructose-fed rats with metabolic syndrome. It also suppressed hepatic inflammatory signaling activation by reducing protein levels of phosphorylation of nuclear factor-kappa B p65 (p-NF-κB p65), inhibitor of nuclear factor kappa-B kinase α/β (p-IKKα/β) and inhibitor of NF-κB α (p-IκBα) as well as nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC) and Caspase-1 in rats, being consistent with its reduction of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and IL-6 levels...
May 16, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28525267/the-supernatant-from-hepatocyte-cultures-with-drugs-that-cause-idiosyncratic-liver-injury-activates-macrophage-inflammasomes
#8
Ryuji Kato, Jack Uetrecht
There is increasing evidence that most idiosyncratic drug-induced liver injury (IDILI) is immune mediated, and in most cases reactive metabolites appear to be responsible for induction of this immune response. Reactive metabolites can cause cell damage with the release of damage-associated molecular patterns (DAMPs), which is thought to be involved in immune activation. Presumably the reason that the liver is a common target of idiosyncratic drug reactions is because it is the major site of drug metabolism and reactive metabolite formation...
May 19, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28521881/acute-fasting-inhibits-central-caspase-1-activity-reducing-anxiety-like-behavior-and-increasing-novel-object-and-object-location-recognition
#9
Albert E Towers, Maci L Oelschlager, Jay Patel, Stephen J Gainey, Robert H McCusker, Gregory G Freund
BACKGROUND: Inflammation within the central nervous system (CNS) is frequently comorbid with anxiety. Importantly, the pro-inflammatory cytokine most commonly associated with anxiety is IL-1β. The bioavailability and activity of IL-1β are regulated by caspase-1-dependent proteolysis vis-a-vis the inflammasome. Thus, interventions regulating the activation or activity of caspase-1 should reduce anxiety especially in states that foster IL-1β maturation. METHODS: Male C57BL/6j, C57BL/6j mice treated with the capase-1 inhibitor biotin-YVAD-cmk, caspase-1 knockout (KO) mice and IL-1R1 KO mice were fasted for 24h or allowed ad libitum access to food...
June 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28518140/a-mirna-101-3p-bim-axis-as-a-determinant-of-serum-deprivation-induced-endothelial-cell-apoptosis
#10
Ji-Hee Kim, Dong-Keon Lee, Joohwan Kim, Seunghwan Choi, Wonjin Park, Kwon-Soo Ha, Tae-Hoon Kim, Jongseon Choe, Moo-Ho Won, Young-Guen Kwon, Young-Myeong Kim
Serum deprivation or withdrawal induces apoptosis in endothelial cells, resulting in endothelial cell dysfunction that is associated with cardiovascular disease. However, there is still limited information on the role of miRNA in serum deprivation-induced apoptosis. Here we found that serum deprivation increased caspase-dependent apoptosis through miRNA-101-3p downregulation, without altering expression of its host gene RNA 3'-terminal phosphate cyclase-like 1, which was highly correlated with suppressed expression levels of Dicer and Argonaute 2 (Ago2), indicating that miR-101-3p is post-transcriptionally elevated in serum-deprived conditions...
May 18, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28516117/reconstruction-of-the-mouse-inflammasome-system-in-hek293t-cells
#11
Hexin Shi, Anne Murray, Bruce Beutler
The NLRP3 (NLR family, Pyrin domain containing 3) inflammasome is a multiprotein complex comprised of NLRP3, pro-caspase-1, the adaptor protein apoptosis-associated speck-like protein containing a CARD (ASC), and the protein kinase NIMA related kinase 7 (NEK7) (Shi et al., 2016; He et al., 2016; Schmid-Burgk et al., 2016). When cells are exposed to microbes and/or danger signals, the inflammasome assembles and serves as a platform for the activation of caspase-1. Caspase-1 activation promotes the processing and secretion of the pro-inflammatory cytokines interleukin-1β (IL-1β), IL-18, and IL-33 as well as pyroptosis induction (Gross et al...
November 5, 2016: Bio-protocol
https://www.readbyqxmd.com/read/28516116/asc-particle-induced-peritonitis
#12
Lucia de Almeida, Andrea Dorfleutner, Christian Stehlik
In response to pathogen infection and tissue damage, inflammasome sensors such as NLRP3 and AIM2 are activated, which triggers PYRIN domain (PYD)-mediated ASC nucleation, followed by self-perpetuating ASC polymerization, which ultimately culminates in caspase-1 activation, interleukin (IL)-1β and IL-18 processing and release and pyroptosis (Ratsimandresy et al., 2013; Cai et al., 2014). Inflammasomes release not only cytokines, but also the polymeric ASC danger particles (pASC) by pyroptosis, which perpetuate and propagate inflammasome responses to bystander cells to engage cell intrinsic ASC and caspase-1 (Baroja-Mazo et al...
October 5, 2016: Bio-protocol
https://www.readbyqxmd.com/read/28508104/quercetin-inhibits-gout-arthritis-in-mice-induction-of-an-opioid-dependent-regulation-of-inflammasome
#13
Kenji W Ruiz-Miyazawa, Larissa Staurengo-Ferrari, Sandra S Mizokami, Talita P Domiciano, Fabiana T M C Vicentini, Doumit Camilios-Neto, Wander R Pavanelli, Phileno Pinge-Filho, Flávio A Amaral, Mauro M Teixeira, Rubia Casagrande, Waldiceu A Verri
We investigated the anti-inflammatory and analgesic effects of quercetin in monosodium urate crystals (MSU)-induced gout arthritis, and the sensitivity of quercetin effects to naloxone, an opioid receptor antagonist. Mice were treated with quercetin, and mechanical hyperalgesia was assessed at 1-24 h after MSU injection. In vivo, leukocyte recruitment, cytokine levels, oxidative stress, NFκB activation, and gp91(phox) and inflammasome components (NLRP3, ASC, Pro-caspase-1, and Pro-IL-1β) mRNA expression by qPCR were determined in the knee joints at 24 h after MSU injection...
May 15, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28507328/pro-inflammatory-ca-activated-k-channels-are-inhibited-by-hydroxychloroquine
#14
María Eugenia Schroeder, Sofía Russo, Carlos Costa, Juliana Hori, Inés Tiscornia, Mariela Bollati-Fogolín, Darío S Zamboni, Gonzalo Ferreira, Ernesto Cairoli, Marcelo Hill
Antimalarials have demonstrated beneficial effects in Systemic Lupus Erithematosus and Rheumatoid Arthritis. However, the mechanisms and the molecular players targeted by these drugs remain obscure. Although hydroxychloroquine (HCQ) is a known ion channel inhibitor, this property has not been linked to its anti-inflammatory effects. We aimed to study whether HCQ inhibits pro-inflammatory ion channels. Electrophysiology experiments demonstrated that HCQ inhibited Ca(++)-activated K(+) conductance in THP-1 macrophages in a dose-dependent manner...
May 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28507179/elevated-expression-of-the-nlrp3-inflammasome-and-its-correlation-with-disease-activity-in-adult-onset-still-disease
#15
Chia-Wei Hsieh, Yi-Ming Chen, Chi-Chen Lin, Kuo-Tung Tang, Hsin-Hua Chen, Wei-Ting Hung, Kuo-Lung Lai, Der-Yuan Chen
OBJECTIVE: The dysregulation of the NLRP3 (NLR containing a pyrin domain) inflammasome is involved in autoinflammatory diseases. Adult-onset Still disease (AOSD) is regarded as an autoinflammatory disease. However, the pathogenic involvement of NLRP3 inflammasome in AOSD remains unclear and NLRP3 activators in AOSD are currently unknown. METHODS: The mRNA expression of NLRP3 inflammasome signaling in peripheral blood mononuclear cells (PBMC) from 34 patients with AOSD and 14 healthy subjects was determined using quantitative-PCR (qPCR)...
May 15, 2017: Journal of Rheumatology
https://www.readbyqxmd.com/read/28506683/the-caspase-1-inhibitor-card18-is-specifically-expressed-during-late-differentiation-of-keratinocytes-and-its-expression-is-lost-in-lichen-planus
#16
Haihong Qin, Jiang Jin, Heinz Fischer, Michael Mildner, Maria Gschwandtner, Veronika Mlitz, Leopold Eckhart, Erwin Tschachler
BACKGROUND: CARD18 contains a caspase recruitment domain (CARD) via which it binds to caspase-1 and thereby inhibits caspase-1-mediated activation of the pro-inflammatory cytokine interleukin (IL)-1β. OBJECTIVES: To determine the expression profile and the role of CARD18 during differentiation of keratinocytes and to compare the expression of CARD18 in normal skin and in inflammatory skin diseases. METHODS: Human keratinocytes were induced to differentiate in monolayer and in 3D skin equivalent cultures...
May 1, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28503820/the-p2x7-receptor-nlrp3-inflammasome-complex-predicts-the-development-of-non-hodgkin-s-lymphoma-in-sjogren-s-syndrome-a-prospective-observational-single-center-study
#17
Chiara Baldini, Eleonora Santini, Chiara Rossi, Valentina Donati, Anna Solini
BACKGROUND: P2X7 receptor (P2X7R), trigger of acute inflammatory responses via the NLRP3 inflammasome, is hyperfunctioning in patients with Sjogren Syndrome (SS), where it stimulates IL-18 production. Some patients with SS develop a mucosa-associated lymphoid tissue non-Hodgkin's lymphoma (MALT-NHL). OBJECTIVES: To prospectively evaluate the involvement and the putative prognostic role of this inflammatory pathway in the development of MALT-NHL. METHODS: 147 women with SS have been prospectively followed for a mean of 52 months, relating the expression and function of the P2X7R-inflammasome axis in salivary glands and circulating lymphomonocytes to the prognosis and the degree of the disease...
May 15, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28502296/-recombinant-legionella-pneumophila-flagella-protein-a-rflaa-induces-the-secretion-of-il-6-and-il-1%C3%AE-in-raw264-7-cells-in-vitro
#18
Lijuan Jia, Xiuqin Cao, Zhiwei Yang
Objective To investigate the effect of recombinant Legionella pneumophila flagella protein A (rflaA) on the secretion of interleukin-6 (IL-6) and interleukin-1β (IL-1β) by RAW264.7 macrophage and the possible mechanism. Methods RAW264.7 cells were treated with 0.000, 0.125, 0.250, 0.500, 1.000, 2.000, 4.000 and 8.000 μg/mL rflaA to determine the EC50 of rflaA using CCK-8 assay. Secretion of IL-6 and IL-1β were measured by ELISA at 24, 36 and 48 hours after treatment of the cells with 0.04, 0.08 and 0.16 μg/mL rflaA...
May 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28498362/caspases-and-their-substrates
#19
REVIEW
Olivier Julien, James A Wells
Protease biology is intimately linked to the functional consequences of substrate cleavage events. Human caspases are a family of 12 fate-determining cysteine proteases that are best known for driving cell death, either apoptosis or pyroptosis. More recently, caspases have been shown to be involved in other cellular remodeling events as well including stem cell fate determination, spermatogenesis, and erythroid differentiation. Recent global proteomics methods enable characterization of the substrates that caspases cleave in live cells and cell extracts...
May 12, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28497417/purinergic-p2x7-receptor-functional-genetic-polymorphisms-are-associated-with-the-susceptibility-to-osteoporosis-in-chinese-postmenopausal-women
#20
Hong Xu, Chengxin Gong, Luling He, Shenqiang Rao, Xingzi Liu, Yijun Nie, Changle Liu, Tao Li, Lu Ding, Yunming Tu, Yuping Yang, Fangfang Hu, Yongfang Fan, Hui Wang, Shuo Wang, Chaopeng Xiong, Peipei Zhong, Lan Tang, Shangdong Liang
Osteoporosis (OP) is a major public health problem worldwide. Genetic factors are considered to be major contributors to the pathogenesis of OP. The purinergic P2X7 receptor (P2X7R) has been shown to play a role in the regulation of osteoblast and osteoclast activity and has been considered as an important candidate gene for OP. A case-control study was performed to investigate the associations of functional single nucleotide polymorphisms (SNPs) in the P2X7R gene (rs2393799, rs7958311, rs1718119, rs2230911, and rs3751143) with susceptibility to OP in 400 Chinese OP patients and 400 controls...
May 11, 2017: Purinergic Signalling
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