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https://www.readbyqxmd.com/read/28636595/nlrp9b-inflammasome-restricts-rotavirus-infection-in-intestinal-epithelial-cells
#1
Shu Zhu, Siyuan Ding, Penghua Wang, Zheng Wei, Wen Pan, Noah W Palm, Yi Yang, Hua Yu, Hua-Bing Li, Geng Wang, Xuqiu Lei, Marcel R de Zoete, Jun Zhao, Yunjiang Zheng, Haiwei Chen, Yujiao Zhao, Kellie A Jurado, Ningguo Feng, Liang Shan, Yuval Kluger, Jun Lu, Clara Abraham, Erol Fikrig, Harry B Greenberg, Richard A Flavell
Rotavirus, a leading cause of severe gastroenteritis and diarrhoea in young children, accounts for around 215,000 deaths annually worldwide. Rotavirus specifically infects the intestinal epithelial cells in the host small intestine and has evolved strategies to antagonize interferon and NF-κB signalling, raising the question as to whether other host factors participate in antiviral responses in intestinal mucosa. The mechanism by which enteric viruses are sensed and restricted in vivo, especially by NOD-like receptor (NLR) inflammasomes, is largely unknown...
June 21, 2017: Nature
https://www.readbyqxmd.com/read/28633109/endothelial-nlrp3-inflammasome-activation-and-arterial-neointima-formation-associated-with-acid-sphingomyelinase-during-hypercholesterolemia
#2
Saisudha Koka, Min Xia, Yang Chen, Owais M Bhat, Xinxu Yuan, Krishna M Boini, Pin-Lan Li
The NLRP3 inflammasome has been reported to be activated by atherogenic factors, whereby endothelial injury and consequent atherosclerotic lesions are triggered in the arterial wall. However, the mechanisms activating and regulating NLRP3 inflammasomes remain poorly understood. The present study tested whether acid sphingomyelinase (ASM) and ceramide associated membrane raft (MR) signaling platforms contribute to the activation of NLRP3 inflammasomes and atherosclerotic lesions during hypercholesterolemia. We found that 7-ketocholesterol (7-Keto) or cholesterol crystal (ChC) markedly increased the formation and activation of NLRP3 inflammasomes in mouse carotid arterial endothelial cells (CAECs), as shown by increased colocalization of NLRP3 with ASC or caspase-1, enhanced caspase-1 activity and elevated IL-1β levels, which were markedly attenuated by mouse Asm siRNA, ASM inhibitor- amitriptyline, and deletion of mouse Asm gene...
June 15, 2017: Redox Biology
https://www.readbyqxmd.com/read/28631213/the-constitutive-protease-release-by-primary-human-acute-myeloid-leukemia-cells
#3
Maria Honnemyr, Øystein Bruserud, Annette K Brenner
INTRODUCTION: Acute myeloid leukemia (AML) cells show constitutive release of matrix metalloproteases and their inhibitors. We now investigated this constitutive release of protease/protease regulators associated with carcinogenesis (ADAM12, uPA, cystatin B), angiogenesis (serpin E1, uPA, CD147), cancer cell migration (uPA, cystatin C), coagulation (ADAM TS13, serpin C1), inflammation (fetuin A, caspase 1, cystatin C), monocytic differentiation (CFD) or regulation of hematopoiesis (neutrophil elastase)...
June 19, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28619472/gasdermins-effectors-of-pyroptosis
#4
REVIEW
Stephen B Kovacs, Edward A Miao
Pyroptosis is a form of lytic programmed cell death initiated by inflammasomes, which detect cytosolic contamination or perturbation. This drives activation of caspase-1 or caspase-11/4/5, which cleave gasdermin D, separating its N-terminal pore-forming domain (PFD) from the C-terminal repressor domain (RD). The PFD oligomerizes to form large pores in the membrane that drive swelling and membrane rupture. Gasdermin D is one of six (in humans) gasdermin family members; several other gasdermins have also been shown to form pores that cause pyroptosis after cleavage to activate their PFDs...
June 12, 2017: Trends in Cell Biology
https://www.readbyqxmd.com/read/28617316/globular-adiponectin-inhibits-lipopolysaccharide-primed-inflammasomes-activation-in-macrophages-via-autophagy-induction-the-critical-role-of-ampk-signaling
#5
Mi Jin Kim, Eun Hye Kim, Nirmala TiliJa Pun, Jae-Hoon Chang, Jung-Ae Kim, Jee-Heon Jeong, Dong Young Choi, Sang-Hyun Kim, Pil-Hoon Park
The inflammasome acts as a key platform for the activation of pro-inflammatory cytokines. Adiponectin exhibits potent anti-inflammatory properties. However, the effect of adiponectin on the modulation of the inflammasome has not been explored. Herein, we show that globular adiponectin (gAcrp) suppressed lipopolysaccharide (LPS)-primed inflammasomes activation in murine peritoneal macrophages judged by prevention of interleukin-1β (IL-1β) maturation, caspase-1 activation, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) speck formation, and pyroptotic cell death...
June 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28616734/di-2-pyridylketone-4-4-dimethyl-3-thiosemicarbazone-dp44mt-an-anticancer-agent-exerts-an-anti-inflammatory-effect-in-activated-human-mast-cells
#6
Sun-Young Nam, Na-Ra Han, Kyoung Wan Yoon, Hyung-Min Kim, Hyun-Ja Jeong
OBJECTIVE: Inflammation has been closely associated with the development and progression of cancer. Previously, we reported that mast cells play a critical role in tumor growth. The purpose of this study is to investigate the anti-inflammatory effect of an anticancer agent, di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT), on an activated human mast cell line, in this case HMC-1 cells. METHODS: We evaluated the effect and specific molecular mechanism of Dp44mT on phorbol 12-myristate 13-acetate and calcium ionophore A23187 (PMACI) using HMC-1 cells...
June 14, 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/28614830/expression-of-tlr2-nod1-and-nod2-and-the-nlrp3-inflammasome-in-renal-tubular-epithelial-cells-of-male-versus-female-mice
#7
Sean E DeWolf, Alana A Shigeoka, Andrew Scheinok, Sashi G Kasimsetty, Alexander K Welch, Dianne B McKay
BACKGROUND: Gender-biased outcomes are associated with acute kidney injury (AKI) and human and animal studies have shown that females are preferentially protected from renal ischemia. However, the reason for this is not known. One clue might lie with pattern recognition receptors (PRRs), which are triggers of ischemic injury when ligated by molecules in the ischemic milieu. Several PRR families are expressed by renal tubular epithelial cells (RTEs) and incite cell death signaling and production of pro-inflammatory molecules...
June 15, 2017: Nephron
https://www.readbyqxmd.com/read/28614717/microbiota-normalization-reveals-that-canonical-caspase-1-activation-exacerbates-chemically-induced-intestinal-inflammation
#8
Adrian J Błażejewski, Sophie Thiemann, Alexander Schenk, Marina C Pils, Eric J C Gálvez, Urmi Roy, Ulrike Heise, Marcel R de Zoete, Richard A Flavell, Till Strowig
Inflammasomes play a central role in regulating intestinal barrier function and immunity during steady state and disease. Because the discoveries of a passenger mutation and a colitogenic microbiota in the widely used caspase-1-deficient mouse strain have cast doubt on previously identified direct functions of caspase-1, we reassessed the role of caspase-1 in the intestine. To this end, we generated Casp1(-/-) and Casp11(-/-) mice and rederived them into an enhanced barrier facility to standardize the microbiota...
June 13, 2017: Cell Reports
https://www.readbyqxmd.com/read/28612844/nlrp3-inflammasome-pathway-has-a-critical-role-in-the-host-immunity-against-clinically-relevant-acinetobacter-baumannii-pulmonary-infection
#9
N Dikshit, S D Kale, H J Khameneh, V Balamuralidhar, C Y Tang, P Kumar, T P Lim, T T Tan, A L Kwa, A Mortellaro, B Sukumaran
The opportunistic Gram-negative bacterium Acinetobacter baumannii (AB) is a leading cause of life-threatening nosocomial pneumonia. Outbreaks of multidrug resistant (MDR)-AB belonging to international clones (ICs) I and II with limited treatment options are major global health threats. However, the pathogenesis mechanisms of various AB clonal groups are understudied. Although inflammation-associated interleukin-1β (IL-1β) levels and IL-1 receptor antagonist polymorphisms were previously implicated in MDR-AB-related pneumonia in patients, whether inflammasomes has any role in the host defense and/or pathogenesis of clinically relevant A...
June 14, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28606793/mir-20b-inhibits-mycobacterium-tuberculosis-induced-inflammation-in-the-lung-of-mice-through-targeting-nlrp3
#10
Jun Lou, Yongli Wang, Zhimin Zhang, Weiqiang Qiu
Tuberculosis (TB) is one of immune-related disorders. Although dysregulation of miRNAs has been implicated in innate and adaptive immune response, the specific effect of miR-20b on TB has not been documented. In this study, downregulation of miR-20b and upregulation of NLRP3 were observed in macrophages of TB patients, increased levels of inflammatory factors secretion were observed in serum of TB patients. Next, we established a TB mice model by using M. tuberculosis infection and intravenous injection of miR-20b mimic...
June 9, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28605710/chronic-dexamethasone-treatment-results-in-hippocampal-neurons-injury-due-to-activate-nlrp1-inflammasome-in-vitro
#11
Biqiong Zhang, Yaodong Zhang, Tanzhen Xu, Yanyan Yin, Rongrong Huang, Yuchan Wang, Junyan Zhang, Dake Huang, Weizu Li
Neuroinflammation mediated by NLRP-1 inflammasome plays an important role in the pathogenesis of neurodegeneration diseases such as Alzheimer's disease (AD). Chronic glucocorticoids (GCs) exposure has deleterious effect on the structure and function of neurons and was found to be correlated with development and progression of AD. We hypothesize that chronic glucocorticoids may down-regulate the expression of glucocorticoids receptor (GR) and activate NLRP-1 inflammasome in hippocampal neurons, which may promote neuroinflammation and induce neuronal injury...
June 9, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28605578/roflupram-a-phosphodiesterase-4-inhibitior-suppresses-inflammasome-activation-through-autophagy-in-microglial-cells
#12
Tingting You, Yu-Fang Cheng, Jiahong Zhong, Bingtian Bi, Bingqing Zeng, Wenhua Zheng, Hai-Tao Wang, Jiang-Ping Xu
Inhibition of phosphodiesterase 4 (PDE4) suppressed the inflammatory responses in the brain. However, the underlying mechanisms are poorly understood. Roflupram (ROF) is a novel PDE4 inhibitor. In the present study, we found that ROF enhanced the level of microtubule-associated protein 1 light chain 3 II (LC3-II) and decreased p62 in microglial BV-2 cells. Enhanced fluorescent signals were observed in BV-2 cells treated with ROF by Lysotracker red and acridine orange staining. In addition, immunofluorescence indicated a significant increase in punctate LC3...
June 12, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28599247/inflammasomes-the-cardinal-pathology-mediators-are-activated-by-pathogens-allergens-and-mutagens-a-critical-review-with-focus-on-nlrp3
#13
REVIEW
Seema Patel
Inflammation is a pivotal defense system of body. Unfortunately, when homeostasis falters, the same inflammatory mechanism acts as a double-edged sword, and turns offensive, paving the path for a broad array of pathologies. A multi-protein complex termed as inflammasome perceives the PAMPs (pathogen associated molecular patterns) and DAMPs (danger associated molecular patterns), executing immune responses. This activation predominantly encompasses the elaboration of effector cytokines IL-1β, IL-18, and the cysteine proteases (caspase 1 and 11)...
June 6, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28598075/-the-protective-effect-of-tanshinone-iia-on-oxygen-glucose-deprivation-and-reperfusion-injury-of-microgliathrough-the-nlrp3-inflammatory-signaling-pathway
#14
Lin Cai, Xiao-Bo Yi, Li-Bang Yuan, Gu Gong
OBJECTIVES: To investigate the protective effect of Tanshinone IIA (TSA) on oxygen-glucose deprivation and reperfusion (OGD/R) injury of BV-2 cell and its NLRP3 inflammatory signaling pathway. METHODS: The highest expression level of NLPR3 in BV-2 cells was detected by Western blot after oxygen-glucose deprivation (OGD) for 3 h and reperfusion for different time, to determine the most suitable reperfusion time. Cell viability of TSA (0-2.5 ug/mL) treatment was detected by CCK8 assay to determine the maximum effect concentration of TSA...
September 2016: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28598074/-sodium-ferulate-attenuates-oxidative-stressvia-suppressing-nalp3-inflammasome-and-erk-signal-pathway
#15
Xiao-Lin Wei, Min Xie, Gao-Yan He
OBJECTIVES: Study the gene and protein expression of NACHT-PYD-containing protein 3 (NALP3) inflammasome and extracellular regulated protein kinase (ERK), the intervention effects of sodium ferulate (SF) in human lung epithelial cells A549 under oxidative stress, and to investigate the possible mechanism. METHODS: Human lung epithelial cells A549 cultured in vitro were divided into 6 groups, including control group,H₂O₂(200 umol/L) group, SF group (400 ug/mL), caspase-1 blockers (Z-VAD) group (Z-VAD 20 umol/L+H₂O₂200 umol/L), ERK blockers (PD98059) group (PD98059 50 umol/L+H₂O₂ 200 umol/L), and SF+H₂O₂ group (SF 400 ug/mL+H₂O₂ 200 umol/L)...
September 2016: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28596375/nlrp3-inflammasome-inhibition-by-mcc950-reduces-atherosclerotic-lesion-development-in-apolipoprotein-e-deficient-mice
#16
Thomas van der Heijden, Eva Kritikou, Wouter Venema, Janine van Duijn, Peter J van Santbrink, Bram Slütter, Amanda C Foks, Ilze Bot, Johan Kuiper
OBJECTIVE: Inflammasomes are multiprotein complexes, and their activation has been associated with cardiovascular disease. Inflammasome activation leads to secretion of caspase-1 by innate immune cells, resulting in the activation of interleukin-1β. Recently, a potent and selective inhibitor of the NLRP3 inflammasome, MCC950, was described. In this study, we investigated the effect of MCC950 on atherosclerotic lesion development in apoE(-/-) mice. APPROACH AND RESULTS: First, we determined the efficacy of MCC950 in vitro...
June 8, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28593173/a-type-iii-effector-nlef-from-ehec-inhibits-epithelial-inflammatory-cell-death-by-targeting-caspase-4
#17
Ting Song, Kaiwu Li, Wei Zhou, Jing Zhou, Yuan Jin, Hongmei Dai, Tingting Xu, Mingda Hu, Hongguang Ren, Junjie Yue, Long Liang
Enterohemorrhagic E. coli (EHEC) is a highly pathogenic bacterial strain capable of inducing severe gastrointestinal disease. Here, we show that EHEC uses the T3SS effector NleF to counteract the host inflammatory response by dampening caspase-4-mediated inflammatory epithelial cell death and by preventing the production of IL-1β. The other two inflammatory caspases, caspase-1 and caspase-5, are not involved in EHEC ΔnleF-induced inflammatory cell death. We found that NleF not only interrupted the heterodimerization of caspase-4-p19 and caspase-4-p10, but also inhibited the interaction of caspase-1 and caspase-4...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28592027/-glyburide-prevents-pulmonary-artery-smooth-muscle-cell-proliferation-and-migration-via-inhibiting-nlrp3-activation
#18
Y F Liu, W Wang, T Liu, W Zhang, J Liu, J Wang
Objective: To investigate whether glyburide prevents platelet-derived growth factor (PDGF) induced pulmonary artery smooth muscle cells(PASMCs) proliferation and migration via inhibiting nucleotide binding domain leucine-rich repeat-containing receptors protein 3(NLRP3) inflammasome activation. Methods: PASMCs were divided into 4 groups: control group, glyburide group, PDGF group and PDGF+ glyburide group. Cell proliferation and migration were assessed by MTT and Transwell respectively. The NLRP3 inflammasome activation was assessed by Western blot...
June 12, 2017: Chinese Journal of Tuberculosis and Respiratory Diseases
https://www.readbyqxmd.com/read/28591554/nlrp3-participates-in-the-regulation-of-emt-in-bleomycin-induced-pulmonary-fibrosis
#19
Rui Tian, Yong Zhu, Jiayi Yao, Xiaoxiao Meng, Jinfeng Wang, Hui Xie, Ruilan Wang
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and irreversible lung disease. Studies have shown that epithelial-mesenchymal transition (EMT) plays an important role in the development of IPF. The NLRP3 inflammasome is reported to be activated and play an important role in many respiratory diseases. However, whether the NLRP3 inflammasome is activated in alveolar epithelial cells as well as the regulatory role of NLRP3 in EMT have not been reported. In this study, we transfected NLRP3 siRNA into A549 and RLE-6TN cells and treated them with bleomycin (BLM) for 24h...
June 4, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28589946/elevated-prostaglandin-e2-post-bone-marrow-transplant-mediates-interleukin-1%C3%AE-related-lung-injury
#20
G J Martínez-Colón, Q M Taylor, C A Wilke, A B Podsiad, B B Moore
Hematopoietic stem cell transplant (HSCT) treats or cures a variety of hematological and inherited disorders. Unfortunately, patients who undergo HSCT are susceptible to infections by a wide array of opportunistic pathogens. Pseudomonas aeruginosa bacteria can have life-threatening effects in HSCT patients by causing lung pathology that has been linked to high levels of the potent pro-inflammatory cytokine, interleukin-1β (IL-1β). Using a murine bone marrow transplant (BMT) model, we show that overexpression of prostaglandin E2 (PGE2) post-BMT signals via EP2 or EP4 to induce cyclic adenosine monophosphate (cAMP), which activates protein kinase A or the exchange protein activated by cAMP (Epac) to induce cAMP response element binding-dependent transcription of IL-1β leading to exacerbated lung injury in BMT mice...
June 7, 2017: Mucosal Immunology
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