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https://www.readbyqxmd.com/read/28637102/-the-progression-of-liver-fibrosis-in-non-alcoholic-fatty-liver-disease
#1
REVIEW
Moon Young Kim
Understanding the pathogenesis of non-alcoholic steatohepatitis (NASH) and its fibrosis progression is still evolving. Nonetheless, current evidence suggests that mechanisms involved are very complex parallel processes with multiple metabolic factors. Lipotoxicity related with excess saturated free fatty acids, obesity, and insulin resistance acts as the central driver of cellular injury via oxidative stress. Hepatocyte apoptosis and/or senescence are also contribute to the activation of inflammasome via various intra- and inter-cellular signaling mechanisms that lead to fibrosis...
June 25, 2017: Korean Journal of Gastroenterology, Taehan Sohwagi Hakhoe Chi
https://www.readbyqxmd.com/read/28636595/nlrp9b-inflammasome-restricts-rotavirus-infection-in-intestinal-epithelial-cells
#2
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/28635590/imbalance-between-innate-antiviral-and-pro-inflammatory-immune-responses-may-contribute-to-different-outcomes-involving-low-and-highly-pathogenic-avian-influenza-h5n3-infections-in-chickens
#3
John Pasick, Sandra Diederich, Yohannes Berhane, Carissa Embury-Hyatt, Wanhong Xu
In order to gain further insight into the early virus-host interactions associated with highly pathogenic avian influenza virus infections in chickens, genome-wide expression profiling of chicken lung and brain was carried out at 24 and 72 h post-inoculation (h p.i.). For this purpose two recombinant H5N3 viruses were utilized, each possessing a polybasic HA0 cleavage site but differing in pathogenicity. The original rH5N3 P0 virus, which has a low-pathogenic phenotype, was passaged six times through chickens to give rise to the derivative rH5N3 P6 virus, which is highly pathogenic (Diederich S, Berhane Y, Embury-Hyatt C, Hisanaga T, Handel K et al...
June 21, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28634425/a-transcriptional-regulatory-role-for-the-membrane-type-1-matrix-metalloproteinase-in-carcinogen-induced-inflammasome-gene-expression
#4
Samuel Sheehy, Borhane Annabi
Signal-transducing functions driven by the cytoplasmic domain of membrane type-1 matrix metalloproteinase (MT1-MMP) are believed to regulate many inflammation-associated cancer cell functions including migration, proliferation, and survival. Aside from upregulation of the inflammation biomarker cyclooxygenase-2 (COX-2) expression, MT1-MMP's role in relaying intracellular signals triggered by extracellular pro-inflammatory cues remains poorly understood. Here, we triggered inflammation in HT1080 fibrosarcoma cells with phorbol-12-myristate-13-acetate (PMA), an inducer of COX-2 and of MT1-MMP...
2017: Gene Regulation and Systems Biology
https://www.readbyqxmd.com/read/28633109/endothelial-nlrp3-inflammasome-activation-and-arterial-neointima-formation-associated-with-acid-sphingomyelinase-during-hypercholesterolemia
#5
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/28631886/nlrp3-expression-and-urinary-hsp72-in-relation-to-biomarkers-of-inflammation-and-oxidative-stress-in-diabetic-nephropathy-patients
#6
Hemat El-Sayed El-Horany, Rania Nagi Abd-Ellatif, Mona Watany, Yasser M Hafez, Hanaa Ibrahim Okda
Diabetic nephropathy (DN) is one of the major causes of end-stage renal disease. Nod-like receptors nucleotide-binding domain and leucine-rich repeat pyrin-3 domain (NLRP3) inflammasome displays a considerable role in the chronic inflammatory state observed in diabetic patients. Urinary heat shock protein 72 (uHSP72) is a sensitive and specific biomarker for the early detection of acute kidney injury. The aim of this study was to evaluate NLRP3 relative gene expression, its correlation with inflammatory and oxidative stress markers, and to assess the value of uHSP72 in the early detection of DN in type 2 diabetic patients with different degrees of DN...
June 20, 2017: IUBMB Life
https://www.readbyqxmd.com/read/28631084/nlrp3-inflammasome-in-inflammatory-bowel-disease-friend-or-foe
#7
EDITORIAL
Ling Liu, Xuhang Li
No abstract text is available yet for this article.
June 19, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28630380/the-immunological-basis-in-the-pathogenesis-of-gout
#8
Junwei Chen, Meng Wu, Jinhua Yang, Jing Wang, Yue Qiao, Xiaofeng Li
Gout is an inflammatory arthritis characterized by red, tender, hot and tumid joints. The development cause and process of gout is very sophisticated; recent studies, notwithstanding, have offered novel perspectives on the mechanism from an immunological viewpoint. The pathological process of gout involves both innate and adaptive immune responses. Other studies have demonstrated that gout development is associated with the presence of monosodium urate (MSU) crystals which serve as a "danger signal" affecting certain immune cells, cytokine production, and effector molecule expression, triggering both types of immune responses...
June 2017: Iranian Journal of Immunology: IJI
https://www.readbyqxmd.com/read/28630327/virus-induced-inflammasome-activation-is-suppressed-by-prostaglandin-d2-dp1-signaling
#9
Rahul Vijay, Anthony R Fehr, Ann M Janowski, Jeremiah Athmer, Dorthea L Wheeler, Matthew Grunewald, Ramakrishna Sompallae, Samarchith P Kurup, David K Meyerholz, Fayyaz S Sutterwala, Shuh Narumiya, Stanley Perlman
Prostaglandin D2 (PGD2), an eicosanoid with both pro- and anti-inflammatory properties, is the most abundantly expressed prostaglandin in the brain. Here we show that PGD2 signaling through the D-prostanoid receptor 1 (DP1) receptor is necessary for optimal microglia/macrophage activation and IFN expression after infection with a neurotropic coronavirus. Genome-wide expression analyses indicated that PGD2/DP1 signaling is required for up-regulation of a putative inflammasome inhibitor, PYDC3, in CD11b(+) cells in the CNS of infected mice...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28630102/the-phenotype-and-function-of-preterm-infant-monocytes-implications-for-susceptibility-to-infection
#10
REVIEW
Emma de Jong, Tobias Strunk, David Burgner, Pascal M Lavoie, Andrew Currie
The extreme vulnerability of preterm infants to invasive microbial infections has been attributed to "immature" innate immune defenses. Monocytes are important innate immune sentinel cells critical in the defense against infection in blood. They achieve this via diverse mechanisms that include pathogen recognition receptor- and inflammasome-mediated detection of microbes, migration into infected tissues, and differentiation into Mϕs and dendritic cells, initiation of the inflammatory cascade by free radicals and cytokine/chemokine production, pathogen clearance by phagocytosis and intracellular killing, and the removal of apoptotic cells...
June 19, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28629999/trimethylamine-n-oxide-prime-nlrp3-inflammasome-via-inhibiting-atg16l1-induced-autophagy-in-colonic-epithelial-cells
#11
Chaochi Yue, Xiangdong Yang, Jun Li, Xiaochao Chen, Xiangdong Zhao, Ye Chen, Yong Wen
Recently, the intricate relationship between Trimethylamine N-oxide (TMAO) and inflammatory bowel disease (IBD) is of growing interest. The NLRP3 inflammasome plays crucial roles in gut homeostasis and determining the severity of inflammation in IBD, however, the precise roles of the NLRP3 inflammasome in IBD are still debated. ATG16L1 mediates the cellular degradative process of autophagy and is considered a critical regulator of inflammation based on its genetic association with IBD. Whether TMAO prime NLRP3 inflammasome via ATG16L1-induced autophagy remains unclear...
June 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28628921/activation-of-cox-2-mpges-1-pge2-cascade-via-nlrp3-inflammasome-contributes-to-albumin-induced-proximal-tubule-cell-injury
#12
Yibo Zhuang, Fei Zhao, Jing Liang, Xu Deng, Yue Zhang, Guixia Ding, Aihua Zhang, Zhanjun Jia, Songming Huang
BACKGROUND/AIMS: The activation of NOD-like receptor family, pyrin domain containing3 (NLRP3) inflammasome has been shown to be positively correlated with the severity of proteinuria in chronic kidney disease (CKD) patients. Prostaglandin E2 (PGE2), an important inflammatory mediator, is also involved in various kidney injuries. The aim of the present study was to investigate the involvement of NLRP3 inflammasome and PGE2 synthetic pathway in albumin-induced renal tubular injury. METHODS: Murine proximal tubular cells (mPTCs) were treated with albumin to induce cell injury...
June 19, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28624931/familial-mediterranean-fever-review-of-the-literature
#13
Mansour Alghamdi
Familial Mediterranean fever (FMF) is the most common monogenic periodic fever syndrome and characterized by recurrent episodes of fever, serositis, arthritis, dermal manifestations, and long-term renal complications. The MEFV gene was described in 1997 as the gene responsible for FMF and is inherited in autosomal recessive manner. It encodes mutated protein pyrin, an important player in the innate immune system and the component of inflammasome which leads to exaggerated inflammatory response through uncontrolled production of interleukin-1...
June 18, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28623945/mir-155-is-overexpressed-in-systemic-sclerosis-fibroblasts-and-is-required-for-nlrp3-inflammasome-mediated-collagen-synthesis-during-fibrosis
#14
Carol M Artlett, Sihem Sassi-Gaha, Jennifer L Hope, Carol A Feghali-Bostwick, Peter D Katsikis
BACKGROUND: Despite the important role that microRNAs (miRNAs) play in immunity and inflammation, their involvement in systemic sclerosis (SSc) remains poorly characterized. miRNA-155 (miR-155) plays a role in pulmonary fibrosis and its expression can be induced with interleukin (IL)-1β. SSc fibroblasts have activated inflammasomes that are integrally involved in mediating the myofibroblast phenotype. In light of this, we investigated whether miR-155 played a role in SSc and if its expression was dependent on inflammasome activation...
June 17, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28623127/the-inhibition-of-nlrp3-signaling-attenuates-liver-injury-in-an-%C3%AE-galactosylceramide-induced-hepatitis-model
#15
Ayumu Kanbe, Hiroyasu Ito, Yukari Omori, Akira Hara, Mitsuru Seishima
Inflammasomes are involved in innate immune responses. Several NOD-Like receptors (NLRs) participate in the formation of inflammasomes. NACHT, LRR and PYD domains-containing protein 3 (NALP3) belongs to the NLR family and recognizes adenosine triphosphate (ATP), crystals, and Reactive Oxygen Species (ROS). This study examined the effect of inflammasomes on alpha-galactosylceramide (GalCer)-induced liver injury using NALP3-knockout (KO) mice. GalCer administration induced inflammasome activation and IL-1β-maturation...
June 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28621928/aluminum-oxy-hydroxide-nanosticks-synthesized-in-bicontinuous-reverse-microemulsion-have-potent-vaccine-adjuvant-activity
#16
Xu Li, Stephanie Hufnagel, Haiyue Xu, Solange A Valdes, Sachin G Thakkar, Zhengrong Cui, Hugo Celio
Insoluble aluminum salts such as aluminum (oxy)hydroxide are commonly used vaccine adjuvants. Recently, there is evidence suggesting that the adjuvant activity of aluminum salt-based materials is tightly related to their physico-chemical properties, including nanometer-scale size, shape with long aspect ratio, and low degree of crystallinity. Herein, for the first time, the bicontinuous reverse microemulsion (RM) technique was utilized to synthesize stick-like monodisperse aluminum (oxy)hydroxide nanoparticles with a long aspect ratio of ~10, length of ~80 nm and low degree of crystallinity (denoted as Al-nanosticks)...
June 16, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28621333/francisella-requires-dynamic-type-vi-secretion-system-and-clpb-to-deliver-effectors-for-phagosomal-escape
#17
Maj Brodmann, Roland F Dreier, Petr Broz, Marek Basler
Francisella tularensis is an intracellular pathogen that causes the fatal zoonotic disease tularaemia. Critical for its pathogenesis is the ability of the phagocytosed bacteria to escape into the cell cytosol. For this, the bacteria use a non-canonical type VI secretion system (T6SS) encoded on the Francisella pathogenicity island (FPI). Here we show that in F. novicida T6SS assembly initiates at the bacterial poles both in vitro and within infected macrophages. T6SS dynamics and function depends on the general purpose ClpB unfoldase, which specifically colocalizes with contracted sheaths and is required for their disassembly...
June 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28619472/gasdermins-effectors-of-pyroptosis
#18
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/28618410/deletion-of-the-inflammasome-sensor-aim2-mitigates-a%C3%AE-deposition-and-microglial-activation-but-increases-inflammatory-cytokine-expression-in-an-alzheimer-disease-mouse-model
#19
Pei-Jung Wu, Yun-Fen Hung, Hsin-Yu Liu, Yi-Ping Hsueh
OBJECTIVE: Inflammation is clearly associated with Alzheimer disease (AD). Knockout of Nlrp3, a gene encoding an inflammasome sensor, has been shown to ameliorate AD pathology in a mouse model. Because AIM2 is the most dominant inflammasome sensor expressed in mouse brains, here we investigate whether Aim2 deletion also influences the phenotype of a 5XFAD AD mouse model. METHODS: Quantitative RT-PCR, immunostaining, immunoblotting, and behavioral analyses were applied to compare wild-type, Aim2-/-, 5XFAD, and Aim2-/-;5XFAD mice...
June 16, 2017: Neuroimmunomodulation
https://www.readbyqxmd.com/read/28617316/globular-adiponectin-inhibits-lipopolysaccharide-primed-inflammasomes-activation-in-macrophages-via-autophagy-induction-the-critical-role-of-ampk-signaling
#20
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
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