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https://www.readbyqxmd.com/read/28212736/tap73-upregulates-il-1%C3%AE-in-cancer-cells-potential-biomarker-in-lung-and-breast-cancer
#1
Polina Vikhreva, Varvara Petrova, Tarik Gokbulut, Ilias Pestlikis, Mara Mancini, Nicola Di Daniele, Richard A Knight, Gerry Melino, Ivano Amelio
p73 is a transcription factor belonging to the p53 tumour suppressor family. p73(-/-) mice exhibit a range of phenotypes including neurological, reproductive and inflammatory defects. Although the role of p73 in the control of genomic stability explains part of these phenotypes, a clear mechanism of how p73 participates in the inflammatory response is still elusive. Interleukin-1β (IL-1β) has a crucial role in mediating the inflammatory response. Because of its high potency to induce inflammation, the activation and secretion of IL-1β is tightly regulated by large protein complexes, named inflammasomes...
January 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28204821/neutrophil-extracellular-traps-induce-il-1%C3%AE-production-by-macrophages-in-combination-with-lipopolysaccharide
#2
Zhongshuang Hu, Taisuke Murakami, Hiroshi Tamura, Johannes Reich, Kyoko Kuwahara-Arai, Toshiaki Iba, Yoko Tabe, Isao Nagaoka
Upon exposure to invading microorganisms, neutrophils undergo NETosis, a recently identified type of programmed cell death, and release neutrophil extracellular traps (NETs). NETs are described as an antimicrobial mechanism, based on the fact that NETs can trap microorganisms and exhibit bactericidal activity through the action of NET‑associated components. In contrast, the components of NETs have been recognized as damage‑associated molecular pattern molecules (DAMPs), which trigger inflammatory signals to induce cell death, inflammation and organ failure...
January 27, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28197935/anti-inflammatory-effect-of-total-saponin-fraction-from-dioscorea-nipponica-makino-on-gouty-arthritis-and-its-influence-on-nalp3-inflammasome
#3
Qi Zhou, Dong-Hua Yu, Ning Zhang, Shu-Min Liu
OBJECTIVE: To investigate the mechanism of Chinese herbal medicine Dioscorea nipponica for the treatment of monosodium urate crystals-induced gouty arthritis (GA) in rats. METHODS: Sixty male Wistar rats were divided into 6 groups: normal, model, indomethacin and three total saponin (900, 300 and 100 mg/kg) groups. The liver, kidney and serum levels of lysosomal enzymes, antioxidant capacities, and inflammatory factors were measured. In addition, the mRNA and protein levels of the NALP3 inflammasome components in the mononuclear cells of rats' peripheral blood were analyzed using real-time polymerase chain reaction and Western blotting methods, respectively...
February 15, 2017: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28197772/-genetics-of-cryopyrin-associated-periodic-syndrome
#4
REVIEW
J B Kümmerle-Deschner, P Lohse
Familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS) and chronic infantile neurological, cutaneous and articular syndrome/neonatal onset multisystem inflammatory disease (CINCA/NOMID) were originally described as three distinct diseases. After the identification of their common genetic origin in 2001 and 2002, they are now perceived as a continuum of one disease entity and labelled cryopyrin-associated periodic syndromes (CAPS). Mutations in the NLRP3 gene on chromosome 1q44 can be detected in many affected patients...
February 14, 2017: Zeitschrift Für Rheumatologie
https://www.readbyqxmd.com/read/28197335/caspase-8-not-so-silently-deadly
#5
REVIEW
Rebecca Feltham, James E Vince, Kate E Lawlor
Apoptosis is a caspase-dependent programmed form of cell death, which is commonly believed to be an immunologically silent process, required for mammalian development and maintenance of cellular homoeostasis. In contrast, lytic forms of cell death, such as RIPK3- and MLKL-driven necroptosis, and caspase-1/11-dependent pyroptosis, are postulated to be inflammatory via the release of damage associated molecular patterns (DAMPs). Recently, the function of apoptotic caspase-8 has been extended to the negative regulation of necroptosis, the cleavage of inflammatory interleukin-1β (IL-1β) to its mature bioactive form, either directly or via the NLRP3 inflammasome, and the regulation of cytokine transcriptional responses...
January 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28196749/recent-insights-into-the-molecular-mechanisms-underlying-pyroptosis-and-gasdermin-family-functions
#6
REVIEW
Robin A Aglietti, Erin C Dueber
Pyroptosis is an inflammatory form of cell death that not only protects multicellular organisms from invading pathogenic bacteria and microbial infections, but can also lead to sepsis and lethal septic shock if overactivated. Here, we present an overview of recent developments within the pyroptosis field, beginning with the discovery of Gasdermin D (GSDMD) as a substrate of caspase-1 and caspase-11 upon detection of cytosolic lipopolysaccharide (LPS). Cleavage releases the N-terminal domain of GSDMD, causing it to form cytotoxic pores in the plasma membrane of cells...
February 11, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28195949/a-preclinical-translational-study-of-the-cardioprotective-effects-of-plasma-derived-alpha-1-anti-trypsin-in-acute-myocardial-infarction
#7
Adolfo G Mauro, Eleonora Mezzaroma, Carlo Marchetti, Pratyush Narayan, Marco Del Buono, Marialessia Capuano, Andrea Prestamburgo, Simone Catapano, Fadi N Salloum, Antonio Abbate, Stefano Toldo
BACKGROUND: The area of myocardial infarction continues to expand for hours after reperfusion. The injured but viable myocardium may be salvaged if the signals leading to cell death are interrupted. Activation of the caspase-1 inflammasome in the heart shortly after ischemia-reperfusion contributes to the final infarct size. Plasma derived α-1 anti-trypsin (AAT) has shown to inhibit inflammasome formation in vitro and in vivo. To explore the potential translational clinical value of AAT as a therapeutic, we conducted a series of preclinical experiments designed to simulate clinically relevant scenarios...
February 13, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28194406/curcumin-ameliorates-diabetic-nephropathy-by-suppressing-nlrp3-inflammasome-signaling
#8
Miaomiao Lu, Nanchang Yin, Wei Liu, Xiangfei Cui, Shuo Chen, Ermin Wang
Diabetic nephropathy (DN) is the leading cause of end-stage renal disease, partly because of the lack of effective treatments for DN. Curcumin has been shown to exert strong antifibrotic effects in DN, but the underlying mechanisms are not well characterized. In this study, we sought to determine the effects of curcumin on diabetic renal disease in db/db mice and characterize the underlying mechanism of action. We administered curcumin to db/db mice for 16 weeks. In comparison to mock-treated db/db mice, curcumin-treated mice showed diminished renal hypertrophy, reduced mesangial matrix expansion, and a lower level of albuminuria...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28193826/the-nlrp3-inflammasome-has-a-critical-role-in-peritoneal-dialysis-related-peritonitis
#9
Nicolas Hautem, Johann Morelle, Amadou Sow, Cyril Corbet, Olivier Feron, Eric Goffin, François Huaux, Olivier Devuyst
Bacterial peritonitis remains the main cause of technique failure in peritoneal dialysis (PD). During peritonitis, the peritoneal membrane undergoes structural and functional alterations that are mediated by IL-1β The NLRP3 inflammasome is a caspase-1-activating multiprotein complex that links sensing of microbial and stress products to activation of proinflammatory cytokines, including IL-1β The potential roles of the NLRP3 inflammasome and IL-1β in the peritoneal membrane during acute peritonitis have not been investigated...
February 13, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28193569/analysis-of-the-expression-of-nlrp3-and-aim2-in-periapical-lesions-with-apical-periodontitis-and-microbial-analysis-outside-the-apical-segment-of-teeth
#10
Shujun Ran, Bin Liu, Shensheng Gu, Zhe Sun, Jingping Liang
OBJECTIVE: To detect the distribution and expression levels of the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) and the absent in Melanoma 2 (AIM2) inflammasomes in periapical lesions and to analyse the possible microbial stimuli outside of teeth. DESIGN: The distribution of NLRP3 and AIM2 inflammasomes in sixteen periapical lesions was investigated by immunohistochemistry. Meanwhile, the relative gene expression levels of NLRP3 and AIM2 in sixteen periapical lesions and three health periodontal tissue were quantified by real-time polymerase chain reaction (PCR)...
February 6, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/28193546/contribution-of-guanine-nucleotide-exchange-factor-vav2-to-nlrp3-inflammasome-activation-in-mouse-podocytes-during-hyperhomocysteinemia
#11
Sabena M Conley, Justine M Abais-Battad, Xinxu Yuan, Qinghua Zhang, Krishna M Boini, Pin-Lan Li
NADPH oxidase (NOX)-derived reactive oxygen species (ROS) have been demonstrated to mediate the activation of NOD-like receptor protein 3 (NLRP3) inflammasomes in podocytes in response to elevated levels of homocysteine (Hcys). However, it remains unknown how NLRP3 inflammasome activation is triggered by NOX. The present study tested whether the guanine nucleotide exchange factor Vav2 mediates Rac1-mediated NOX activation in response to elevated Hcys leading to NLRP3 inflammasome activation in podocytes and consequent glomerular injury...
February 10, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28192059/inflammasomes-key-mediators-of-lung-immunity
#12
Judie A Howrylak, Kiichi Nakahira
Inflammasomes are key inflammatory signaling platforms that detect microbial substances, sterile environmental insults, and molecules derived from host cells. Activation of the inflammasome promotes caspase-1-mediated secretion of proinflammatory cytokines interleukin (IL)-1β and IL-18 and pyroptosis. Recent developments in this field demonstrate the crucial role of the inflammasome in a wide range of disease models. Although inflammasomes are a crucial part of host defense mechanisms against pathogens, the exuberant immune response resulting from inflammasome activation also contributes to the development of various diseases...
February 10, 2017: Annual Review of Physiology
https://www.readbyqxmd.com/read/28191362/the-anti-inflammatory-effect-of-alpha-1-antitrypsin-in-rhinovirus-infected-human-airway-epithelial-cells
#13
Di Jiang, Reena Berman, Qun Wu, Connor Stevenson, Hong Wei Chu
OBJECTIVE: Excessive airway inflammation is seen in chronic obstructive pulmonary disease (COPD) patients experiencing acute exacerbations, which are often associated with human rhinovirus (HRV) infection. Alpha-1 antitrypsin (A1AT) has anti-inflammatory function in endothelial cells and monocytes, but its anti-inflammatory effect has not been investigated in COPD airway epithelial cells. We determined A1AT's anti-inflammatory function in COPD airway epithelial cells and the underlying mechanisms such as the role of caspase-1...
December 2016: Journal of Clinical & Cellular Immunology
https://www.readbyqxmd.com/read/28191008/the-nlrp3-and-pyrin-inflammasomes-implications-in-the-pathophysiology-of-autoinflammatory-diseases
#14
REVIEW
Carlos de Torre-Minguela, Pablo Mesa Del Castillo, Pablo Pelegrín
Inflammasomes are multiprotein complexes that critically control different aspects of innate and adaptive immunity. Among them we could highlight the release of pro-inflammatory cytokines that induce and maintain the inflammatory response. Usually, inflammasomes result from oligomerization of a nucleotide-binding domain-like receptor (NLR) after sensing different pathogenic or endogenous sterile dangerous signals; however, other proteins such as absent in melanoma 2, retinoic acid-inducible gene I, or pyrin could also form inflammasome platforms...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28182085/maresin-1-mitigates-high-glucose-induced-mouse-glomerular-mesangial-cell-injury-by-inhibiting-inflammation-and-fibrosis
#15
Shi Tang, Chenlin Gao, Yang Long, Wei Huang, Jiao Chen, Fang Fan, Chunxia Jiang, Yong Xu
Background. Inflammation and fibrosis are the important pathophysiologic processes in diabetic nephropathy (DN). Maresin 1 is a potential anti-inflammatory lipid mediator, which has displayed powerful proresolving activities. Aim. We determine whether maresin 1 has protective effect on mouse glomerular mesangial cells (GMCs) induced by high glucose. Methods. We cultured GMCs stimulated by high glucose and categorized as follows: normal glucose group (5.6 mmol/L), high glucose group (30 mmol/L), mannitol group, maresin 1 intervention group (1, 10, and 100 nmol/L), maresin 1 and normal glucose group, and the N-acetylcysteine (NAC) intervention group (10 μmol/L NAC)...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28176796/depurinized-milk-downregulates-rat-thymus-myd88-akt-p38-function-nf-%C3%AE%C2%BAb-mediated-inflammation-caspase-1-activity-but-not-the-endonuclease-pathway-in-vitro-in-vivo-study
#16
Gordana Kocic, Andrej Veljkovic, Hristina Kocic, Miodrag Colic, Dusan Mihajlovic, Katarina Tomovic, Svetlana Stojanovic, Andrija Smelcerovic
The aim of this study was the evaluation of 15 days dietary regimen of depurinized (DP) milk (obtained using our patented technological procedures) or 1.5% fat UHT milk instead of standard chow diet, on rat thymus and bone marrow MyD88/Akt/p38, NF-κB, caspase-1 and endonuclease pathways, in relation to peripheral blood cell composition. To determine whether the reduced mass of the thymus is a consequence of the direct effect of DP/UHT milk on apoptosis of thymocytes, in vitro Annexin-V-FITC/PI assay was performed...
February 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28174758/interferon-alpha-promotes-th1-response-and-epithelial-apoptosis-via-inflammasome-activation-in-human-intestinal-mucosa
#17
Anne Jarry, Florent Malard, Chantal Bou-Hanna, Guillaume Meurette, Mohamad Mohty, Jean-François Mosnier, Christian L Laboisse, Céline Bossard
BACKGOUND & AIMS: Several lines of investigation suggest that interferon (IFN) alpha can alter human intestinal mucosa homeostasis. These include the endogenous production of IFN alpha in celiac disease or inflammatory bowel diseases, as well as the occurrence of intestinal side effects of exogenous IFN alpha used as a therapeutic tool. Here, we present an ex vivo translational approach to investigate the effects of IFN alpha on the human normal intestinal mucosa, as well as its underlying mechanisms...
January 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28169000/regulation-and-functions-of-nlrp3-inflammasome-during-influenza-virus-infection
#18
Teneema Kuriakose, Thirumala-Devi Kanneganti
The NLRP3 inflammasome constitutes a major antiviral host defense mechanism during influenza virus infection. Inflammasome assembly in virus-infected cells facilitates autocatalytic processing of pro-caspase-1 and subsequent cleavage and secretion of proinflammatory cytokines IL-1β and IL-18. The NLRP3 inflammasome is critical for induction of both innate and adaptive immune responses during influenza virus infection. Inflammasome-dependent antiviral responses also regulate immunopathology and tissue repair in the infected lungs...
February 3, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28167322/-nlrp3-inflammasome-blockade-reduces-liver-inflammation-and-fibrosis-in-experimental-nash-in-mice
#19
Auvro R Mridha, Alexander Wree, Avril A B Robertson, Matthew M Yeh, Casey D Johnson, Derrick M Van Rooyen, Fahrettin Haczeyni, Narci C-H Teoh, Christopher Savard, George N Ioannou, Seth L Masters, Kate Schroder, Matthew A Cooper, Ariel E Feldstein, Geoffrey C Farrell
BACKGROUND AND AIMS: NOD-like receptor protein 3 (NLRP3) inflammasome activation occurs in NAFLD. We used the first small molecule NLRP3 inhibitor, MCC950, to test whether inflammasome blockade alters inflammatory recruitment and liver fibrosis in two murine models of steatohepatitis. METHODS: We fed foz/foz and wildtype (Wt) mice atherogenic diet 16 weeks, gavaged MCC950 or vehicle until 24 weeks, then determining NAFLD phenotype. In mice fed methionine/choline deficient (MCD) diet, we gavaged MCC950 or vehicle 6 weeks and determined effects on liver fibrosis...
February 3, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28167279/nlrp3-inflammasome-activation-in-mesenchymal-stem-cells-inhibits-osteogenic-differentiation-and-enhances-adipogenic-differentiation
#20
Linghao Wang, Ke Chen, Xinxing Wan, Fang Wang, Zi Guo, Zhaohui Mo
Osteoporosis is one of the most common skeletal disease featured by osteopenia and adipose accumulation in bone tissue. NLRP3 inflammasome activation is an essential player in aging-related chronic diseases like osteoporosis, particularly due to the causal caspase-1 activation and its correlation to adipose accumulation in bone tissue. Moreover, the expression of anti-aging/senescence SIRT1 was reported to decline along with aging. As the major cellular contributor of bone formation, mesenchymal stem cells (MSCs) are multipotent stem cells processing mutually exclusive differentiatability toward osteocytes or adipocytes...
February 4, 2017: Biochemical and Biophysical Research Communications
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