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https://www.readbyqxmd.com/read/28533778/dnase1l3-regulates-inflammasome-dependent-cytokine-secretion
#1
Guilan Shi, Kennady N Abbott, Wenbo Wu, Russell D Salter, Peter A Keyel
Pediatric-onset systemic lupus erythematosus arises in humans and mice lacking the endonuclease Dnase1L3. When Dnase1L3 is absent, DNA from circulating apoptotic bodies is not cleared, leading to anti-DNA antibody production. Compared to early anti-DNA and anti-chromatin responses, other autoantibody responses and general immune activation in Dnase1L3(-/-) mice are greatly delayed. We investigated the possibility that immune activation, specifically inflammasome activation, is regulated by Dnase1L3. Here, we report that Dnase1L3 inhibition blocked both NLR family, pyrin domain containing 3 (NLRP3) and NLRC4 inflammasome-mediated release of high-mobility group box 1 protein and IL-1β...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28533472/yersinia-pestis-yopk-inhibits-bacterial-adhesion-to-host-cells-by-binding-to-the-extracellular-matrix-adaptor-protein-matrilin-2
#2
Yafang Tan, Wanbing Liu, Qingwen Zhang, Shiyang Cao, Haihong Zhao, Tong Wang, Zhizhen Qi, Yanping Han, Yajun Song, Xiaoyi Wang, Ruifu Yang, Zongmin Du
Pathogenic yersiniae harbor a type III secretion system (T3SS) that injects Yersinia outer protein (Yop) into host cells. YopK has been shown to control Yop translocation and prevent inflammasome recognition of T3SS by the innate immune system. Here, we demonstrate that YopK inhibits bacterial adherence to host cells by binding to the extracellular matrix adaptor protein matrilin-2 (MATN2). YopK binds to MATN2 and deleting the amino acids 91--124 disrupts binding of YopK to MATN2. A yopK null mutant exhibits hyper-adhesive phenotype, which could be responsible for the established Yop hyper-translocation phenotype of yopK mutant...
May 22, 2017: Infection and Immunity
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
#3
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/28532674/cytokine-expression-levels-in-als-a-potential-link-between-inflammation-and-bmaa-triggered-protein-misfolding
#4
Nara Michaelson, Dominic Facciponte, Walter Bradley, Elijah Stommel
Recently, it has been shown that proinflammatory cytokines play a complex and important role in the pathogenesis of many neurological disorders, including amyotrophic lateral sclerosis (ALS). To help facilitate future discoveries and more effective treatment strategies, we highlight the role that both innate and adaptive immune systems play in ALS and summarize the main observations that relate to cytokine expression levels in this disease. Furthermore, we propose a mechanism by which a known neurotoxin, β-N-methylamino-l-alanine (BMAA), may trigger this cytokine expression profile through motor neuron protein misfolding and subsequent NLRP3 (nucleotide-binding domain (NOD)-like receptor protein 3) inflammasome activation...
May 10, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28531279/mechanisms-governing-inflammasome-activation-assembly-and-pyroptosis-induction
#5
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/28528454/new-insights-into-pericarditis-mechanisms-of-injury-and-therapeutic-targets
#6
REVIEW
Bo Xu, Serge C Harb, Paul C Cremer
PURPOSE OF REVIEW: This review article aims to provide a contemporary insight into the pathophysiological mechanisms of and therapeutic targets for pericarditis, drawing distinction between autoinflammatory and autoimmune pericarditis. RECENT FINDINGS: Recent research has focused on the distinction between autoinflammatory and autoimmune pericarditis. In autoinflammatory pericarditis, viruses can activate the sensor molecule of the inflammasome, which results in downstream release of cytokines, such as interleukin-1, that recruit neutrophils and macrophages to the site of injury...
July 2017: Current Cardiology Reports
https://www.readbyqxmd.com/read/28528307/extracellular-atp-is-a-key-modulator-of-alveolar-bone-loss-in-periodontitis
#7
REVIEW
Itzhak Binderman, Nasir Gadban, Avinoam Yaffe
Periodontal diseases are initiated by pathogenic bacterial biofilm activity that induces a host inflammatory cells immune response, degradation of dento gingival fibrous tissue and its detachment from root cementum. It is well accepted, that osteoclastic alveolar bone loss is governed exclusively through secretion of proinflammatory cytokines. Nevertheless, our findings suggest that once degradation of collagen fibers by MMPs occurs, a drop of cellular strains cause immediate release of ATP from marginal gingival fibroblasts, cell deformation and influx of Ca+2...
May 13, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/28528200/sputum-transcriptomics-reveal-up-regulation-of-il-1-receptor-family-members-in-severe-asthma
#8
Christos Rossios, Stelios Pavlidis, Uruj Hoda, Chih-Hsi Kuo, Coen Wiegman, Kirsty Russell, Kai Sun, Matthew J Loza, Frederic Baribaud, Andrew L Durham, Oluwaseun Ojo, Rene Lutter, Anthony Rowe, Aruna Bansal, Charles Auffray, Ana Sousa, Julie Corfield, Ratko Djukanovic, Yike Guo, Peter J Sterk, Kian Fan Chung, Ian M Adcock
BACKGROUND: Sputum analysis in asthma is used to define airway inflammatory processes and may guide therapy. OBJECTIVE: To determine differential gene and protein expression in sputum samples from patients with severe asthma (SA) compared to mild-moderate non-smoking asthmatics (MMA). METHODS: Induced sputum was obtained from non-smoking SA (SAn), smokers/ex-smokers with SA (SAsm), MMA and healthy non-smoking controls. Differential cell counts, microarray analysis of cell pellets and SOMAscan analysis of sputum analytes was performed...
May 17, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28528118/calcium-supplementation-decreases-bcp-induced-inflammatory-processes-in-blood-cells-through-the-nlrp3-inflammasome-down-regulation
#9
Patricia Lagadec, Thierry Balaguer, Florian Boukhechba, Grégory Michel, Sébastien Bouvet-Gerbettaz, Jean-Michel Bouler, Jean-Claude Scimeca, Nathalie Rochet
Interaction of host blood with biomaterials is the first event occurring after implantation in a bone defect. This study aimed at investigating the cellular and molecular consequences arising at the interface between whole blood and biphasic calcium phosphate (BCP) particles. We observed that, due to calcium capture, BCP inhibited blood coagulation, and that this inhibition was reversed by calcium supplementation. Therefore, we studied the impact of calcium supplementation on BCP effects on blood cells. Comparative analysis of BCP and calcium supplemented-BCP (BCP/Ca) effects on blood cells showed that BCP as well as BCP/Ca induced monocyte proliferation, as well as a weak but significant hemolysis...
May 17, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28526809/tumor-cell-specific-aim2-regulates-growth-and-invasion-of-cutaneous-squamous-cell-carcinoma
#10
Mehdi Farshchian, Liisa Nissinen, Elina Siljamäki, Pilvi Riihilä, Minna Piipponen, Atte Kivisaari, Markku Kallajoki, Reidar Grénman, Juha Peltonen, Sirkku Peltonen, Koen D Quint, Jan Nico Bouwes Bavinck, Veli-Matti Kähäri
Cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer. Inflammation is a typical feature in cSCC progression. Analysis of the expression of inflammasome components in cSCC cell lines and normal human epidermal keratinocytes revealed upregulation of the expression of AIM2 mRNA and protein in cSCC cells. Elevated levels of AIM2 mRNA were noted in cSCCs in vivo compared with normal skin. Strong and moderate tumor cell specific expression of AIM2 was detected with immunohistochemistry (IHC) in sporadic human cSCCs in vivo, whereas expression of AIM2 was moderate in cSCC in situ (cSCCIS) and low or absent in actinic keratosis (AK) and normal skin...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28526339/magnesium-isoglycyrrhizinate-blocks-fructose-induced-hepatic-nf-%C3%AE%C2%BAb-nlrp3-inflammasome-activation-and-lipid-metabolism-disorder
#11
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/28525945/the-protective-effect-of-luteolin-on-myocardial-ischemia-reperfusion-i-r-injury-through-tlr4-nf-%C3%AE%C2%BAb-nlrp3-inflammasome-pathway
#12
Xu Zhang, Qianming Du, Yan Yang, Jianing Wang, Shuai Dou, Chao Liu, Junguo Duan
The purpose of the present study was to investigate the effect of Luteolin(Lut) on myocardial ischemia reperfusion injury and explore the underlying mechanism. Myocardial ischemia reperfusion injury (I/R) model was induced with 30min of left anterior descending (LAD) occlusion followed by 24h of reperfusion. In vivo, the rats were randomly divided into 5 groups: (1)Sham, (2)I/R, (3)I/R+Lut(40mg/kg), (4)I/R+Lut(80mg/kg) and (5)I/R+Lut(160mg/kg). In vitro, the H9c2 cells were assigned to five groups: (1)control, (2)hypoxia-reoxygenation(H/R), (3)H/R+Lut(5μM), (4)H/R+Lut(10μM) and (5)H/R+Lut(20μM)...
May 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28525267/the-supernatant-from-hepatocyte-cultures-with-drugs-that-cause-idiosyncratic-liver-injury-activates-macrophage-inflammasomes
#13
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/28523794/mineralocorticoid-receptor-associates-with-pro-inflammatory-bias-in-hippocampus-of-spontaneously-hypertensive-rats
#14
María Elvira Brocca, Luciana Pietranera, Maria Meyer, Analia Lima, Paulina Roig, E Ronald de Kloet, Alejandro F De Nicola
Damage observed in the hippocampus of the adult spontaneously hypertensive rat (SHR) resembles the neuropathology of mineralocorticoid-induced hypertension, supporting a similar endocrine dysfunction in both entities. In this study we have tested the hypothesis that increased expression of the hippocampal mineralocorticoid receptor (MR) in SHR animals is associated with a prevalent expression of pro-inflammatory over anti-inflammatory factors. For this purpose we measured in hippocampus mRNA expression and immunoreactivity of the MR and the glucocorticoid receptor (GR) using qPCR and histochemistry...
May 18, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28523573/activation-of-nlrp3-inflammasome-in-inflammatory-bowel-disease-differences-between-crohn-s-disease-and-ulcerative-colitis
#15
Lazaros-Dimitrios Lazaridis, Aikaterini Pistiki, Evangelos J Giamarellos-Bourboulis, Marianna Georgitsi, Georgia Damoraki, Dimitrios Polymeros, George D Dimitriadis, Konstantinos Triantafyllou
BACKGROUND: NLRP3 inflammasome is a multimolecular cytosol complex that, when activated, contributes to the cleavage of pro-interleukin (IL)-1β to IL-1β. AIMS: To investigate NLRP3 inflammasome activation in inflammatory bowel disease. METHODS: Peripheral blood mononuclear cells from Crohn's disease (CD), ulcerative colitis (UC) patients and controls were stimulated with LPS in the absence or presence of MSU. After incubation, concentrations of IL-1β, IL-6, and TNFα were measured in cell supernatants and concentration of pro-IL-1β was measured in cell lysates...
May 18, 2017: Digestive Diseases and Sciences
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
#16
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
#17
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
#18
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
#19
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/28515391/advanced-glycation-end-products-regulate-interleukin-1%C3%AE-production-in-human-placenta
#20
Kotomi Seno, Saoko Sase, Ayae Ozeki, Hironori Takahashi, Akihide Ohkuchi, Hirotada Suzuki, Shigeki Matsubara, Hisataka Iwata, Takehito Kuwayama, Koumei Shirasuna
Maternal obesity is a major risk factor for pregnancy complications, causing inflammatory cytokine release in the placenta, including interleukin-1β (IL-1β), IL-6, and IL-8. Pregnant women with obesity develop accelerated systemic and placental inflammation with elevated circulating advanced glycation end products (AGEs). IL-1β is a pivotal inflammatory cytokine associated with obesity and pregnancy complications, and its production is regulated by NLR family pyrin domain-containing 3 (NLRP3) inflammasomes...
May 18, 2017: Journal of Reproduction and Development
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