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https://www.readbyqxmd.com/read/28093447/inflammasomes-and-cancer
#1
Rajendra Karki, Si Ming Man, Thirumala-Devi Kanneganti
Inflammation affects all stages of tumorigenesis. A key signaling pathway leading to acute and chronic inflammation is through activation of the caspase-1 inflammasome. Inflammasome complexes are assembled on activation of certain nucleotide-binding domain, leucine-rich repeat-containing proteins (NLR), AIM2-like receptors, or pyrin. Of these, NLRP1, NLRP3, NLRC4, NLRP6, and AIM2 influence the pathogenesis of cancer by modulating innate and adaptive immune responses, cell death, proliferation, and/or the gut microbiota...
January 16, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28062361/redox-signaling-in-the-gastrointestinal-tract
#2
REVIEW
Salvador Pérez, Raquel Taléns-Visconti, Sergio Rius-Pérez, Isabela Finamor, Juan Sastre
Redox signaling regulates physiological self-renewal, proliferation, migration and differentiation in gastrointestinal epithelium by modulating Wnt/β-catenin and Notch signaling pathways mainly through NADPH oxidases (NOXs). In the intestine, intracellular and extracellular thiol redox status modulates the proliferative potential of epithelial cells. Furthermore, commensal bacteria contribute to intestine epithelial homeostasis through NOX1- and dual oxidase 2-derived reactive oxygen species (ROS). The loss of redox homeostasis is involved in the pathogenesis and development of a wide diversity of gastrointestinal disorders, such as Barrett's esophagus, esophageal adenocarcinoma, peptic ulcer, gastric cancer, ischemic intestinal injury, celiac disease, inflammatory bowel disease and colorectal cancer...
January 3, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28056049/asc-induces-apoptosis-via-activation-of-caspase-9-by-enhancing-gap-junction-mediated-intercellular-communication
#3
Masato Kitazawa, Shigeaki Hida, Chifumi Fujii, Shun'ichiro Taniguchi, Kensuke Ito, Tomio Matsumura, Nagisa Okada, Takashi Sakaizawa, Akira Kobayashi, Michiko Takeoka, Shin-Ichi Miyagawa
ASC (apoptosis-associated speck-like protein containing a CARD) is a key adaptor molecule of inflammasomes that mediates inflammatory and apoptotic signals. Aberrant methylation-induced silencing of ASC has been observed in a variety of cancer cells, thus implicating ASC in tumor suppression, although this role remains incompletely defined especially in the context of closely neighboring cell proliferation. As ASC has been confirmed to be silenced by abnormal methylation in HT1080 fibrosarcoma cells as well, this cell line was investigated to characterize the precise role and mechanism of ASC in tumor progression...
2017: PloS One
https://www.readbyqxmd.com/read/28035720/wp1066-suppresses-macrophage-cell-death-induced-by-inflammasome-agonists-independently-of-its-inhibitory-effect-on-stat3
#4
Shino Honda, Daichi Sadatomi, Yasuo Yamamura, Kazutaka Nakashioya, Susumu Tanimura, Kohsuke Takeda
The compound WP1066 was originally synthesized by modifying the structure of AG490, which inhibits the activation of signal transducer and activator of transcription 3 (STAT3) by directly targeting Janus kinases (JAKs). WP1066 exhibits stronger anti-cancer activity than AG490 against malignant glioma and other cancer cells and is regarded as a promising therapeutic agent. By screening a small library of target-known compounds, we identified WP1066 as an inhibitor of macrophage cell death induced by agonists of the NLRP3 inflammasome, an intracellular protein complex required for the processing of the proinflammatory cytokine interleukin (IL)-1β...
December 30, 2016: Cancer Science
https://www.readbyqxmd.com/read/27956668/the-inflammasome-as-a-target-for-pain-therapy
#5
H Zhang, F Li, W-W Li, C Stary, J D Clark, S Xu, X Xiong
The interleukin-1 family of cytokines are potent inducers of inflammation and pain. Proteolytic activation of this family of cytokines is under the control of several innate immune receptors that coordinate to form large multiprotein signalling platforms, termed inflammasomes. Recent evidence suggests that a wide range of inflammatory diseases, cancers, and metabolic and autoimmune disorders, in which pain is a common complaint, may be coordinated by inflammasomes. Activation of inflammasomes results in cleavage of caspase-1, which subsequently induces downstream initiation of several potent pro-inflammatory cascades...
December 2016: British Journal of Anaesthesia
https://www.readbyqxmd.com/read/27928589/genetic-polymorphisms-of-il-18-rs1946518-and-il-1%C3%AE-rs16944-are-associated-with-prognosis-and-survival-of-acute-myeloid-leukemia
#6
Hong Wang, Mingqiang Hua, Shukang Wang, Jie Yu, Chen Chen, Xueyun Zhao, Chen Zhang, Chaoqin Zhong, Ruiqing Wang, Na He, Ming Hou, Daoxin Ma
BACKGROUND: Though the pathogenesis of AML is still unknown, accumulating evidence revealed that immune response plays a vital part in it. NLRP3 inflammasome as a component of immune system has been found related to several cancers. The single nucleotide polymorphisms (SNPs) of NLRP3 inflammasome genes may be related to pathogenesis and prognosis of AML. METHODS AND RESULTS: We determined polymorphisms of NLRP3 (rs35829419), CARD8 (rs2043211), IL-1β (rs16944), IL-18 (rs1946518) and NF-κB -94 ins/del ATTG in de novo AML patients to find out whether they play roles in the susceptibility and severity of AML...
December 7, 2016: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/27895640/%C3%AF-3-polyunsaturated-fatty-acids-as-immunomodulators-in-colorectal-cancer-new-potential-role-in-adjuvant-therapies
#7
REVIEW
Stefania Miccadei, Roberta Masella, Anna Maria Mileo, Sandra Gessani
Diet composition may affect the onset and progression of chronic degenerative diseases, including cancer, whose pathogenesis relies on inflammatory processes. Growing evidence indicates that diet and its components critically contribute to human health, affecting the immune system, secretion of adipokines, and metabolic pathways. Colorectal cancer (CRC) is one of the leading causes of death worldwide. Antineoplastic drugs are widely used for CRC treatment, but drug resistance and/or off-target toxicity limit their efficacy...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27875342/the-multifaceted-roles-of-inflammasome-proteins-in-cancer
#8
Virginie Petrilli
PURPOSE OF REVIEW: Inflammasomes are major actors of the innate immune system, through their regulation of inflammatory caspases and maturation of IL-1β and IL-18. These multiprotein complexes have been shown to play major roles in inflammatory and metabolic diseases and have more recently been implicated in tumor development and dissemination. In this review, we address these recent findings, focusing particularly on colorectal cancer (CRC) initiation and tumor dissemination. RECENT FINDINGS: Based mostly on loss-of-function experiments in mouse models, paradoxical results were obtained as both protumoral and antitumoral activities were reported...
January 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/27842563/novel-extracellular-and-nuclear-caspase-1-and-inflammasomes-propagate-inflammation-and-regulate-gene-expression-a-comprehensive-database-mining-study
#9
Luqiao Wang, Hangfei Fu, Gayani Nanayakkara, Yafeng Li, Ying Shao, Candice Johnson, Jiali Cheng, William Y Yang, Fan Yang, Muriel Lavallee, Yanjie Xu, Xiaoshu Cheng, Hang Xi, Jonathan Yi, Jun Yu, Eric T Choi, Hong Wang, Xiaofeng Yang
BACKGROUND: Caspase-1 is present in the cytosol as an inactive zymogen and requires the protein complexes named "inflammasomes" for proteolytic activation. However, it remains unclear whether the proteolytic activity of caspase-1 is confined only to the cytosol where inflammasomes are assembled to convert inactive pro-caspase-1 to active caspase-1. METHODS: We conducted meticulous data analysis methods on proteomic, protein interaction, protein intracellular localization, and gene expressions of 114 experimentally identified caspase-1 substrates and 38 caspase-1 interaction proteins in normal physiological conditions and in various pathologies...
November 14, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27819292/saponin-based-adjuvants-induce-cross-presentation-in-dendritic-cells-by-intracellular-lipid-body-formation
#10
Martijn H den Brok, Christian Büll, Melissa Wassink, Annemarie M de Graaf, Jori A Wagenaars, Marthe Minderman, Mayank Thakur, Sebastian Amigorena, Eric O Rijke, Carla C Schrier, Gosse J Adema
Saponin-based adjuvants (SBAs) are being used in animal and human (cancer) vaccines, as they induce protective cellular immunity. Their adjuvant potency is a factor of inflammasome activation and enhanced antigen cross-presentation by dendritic cells (DCs), but how antigen cross-presentation is induced is not clear. Here we show that SBAs uniquely induce intracellular lipid bodies (LBs) in the CD11b+ DC subset in vitro and in vivo. Using genetic and pharmacological interference in models for vaccination and in situ tumour ablation, we demonstrate that LB induction is causally related to the saponin-dependent increase in cross-presentation and T-cell activation...
November 7, 2016: Nature Communications
https://www.readbyqxmd.com/read/27786298/targeting-inflammasome-il-1-pathways-for-cancer-immunotherapy
#11
Beichu Guo, Shunjun Fu, Jinyu Zhang, Bei Liu, Zihai Li
The inflammatory microenvironment has been shown to play important roles in various stages of tumor development including initiation, growth, and metastasis. The inflammasome is a critical innate immune pathway for the production of active IL-1β, a potent inflammatory cytokine. Although inflammasomes are essential for host defense against pathogens and contribute to autoimmune diseases, their role in tumor progression remains controversial. Here, our results demonstrate that the inflammasome and IL-1β pathway promoted tumor growth and metastasis in animal and human breast cancer models...
October 27, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27768771/silencing-of-asc-in-cutaneous-squamous-cell-carcinoma
#12
Katharina Meier, Stefan K Drexler, Franziska C Eberle, Karine Lefort, Amir S Yazdi
Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) is an important adaptor protein for inflammasome activation, mediating the secretion of protumorigenic innate cytokines. However, ASC is also known to trigger apoptosis in tumor cells, acting as a tumor-suppressor gene, which is lost in several human cancers. The aim of this study was to evaluate the clinical significance of ASC in human cutaneous squamous cell carcinoma (SCC). Initially, ASC expression was immunohistochemically evaluated in non-metastic and metastatic SCC...
2016: PloS One
https://www.readbyqxmd.com/read/27708283/obesity-associated-nlrc4-inflammasome-activation-drives-breast-cancer-progression
#13
Ryan Kolb, Liem Phan, Nicholas Borcherding, Yinghong Liu, Fang Yuan, Ann M Janowski, Qing Xie, Kathleen R Markan, Wei Li, Matthew J Potthoff, Enrique Fuentes-Mattei, Lesley G Ellies, C Michael Knudson, Mong-Hong Lee, Sai-Ching J Yeung, Suzanne L Cassel, Fayyaz S Sutterwala, Weizhou Zhang
Obesity is associated with an increased risk of developing breast cancer and is also associated with worse clinical prognosis. The mechanistic link between obesity and breast cancer progression remains unclear, and there has been no development of specific treatments to improve the outcome of obese cancer patients. Here we show that obesity-associated NLRC4 inflammasome activation/ interleukin (IL)-1 signalling promotes breast cancer progression. The tumour microenvironment in the context of obesity induces an increase in tumour-infiltrating myeloid cells with an activated NLRC4 inflammasome that in turn activates IL-1β, which drives disease progression through adipocyte-mediated vascular endothelial growth factor A (VEGFA) expression and angiogenesis...
October 6, 2016: Nature Communications
https://www.readbyqxmd.com/read/27697299/transcriptional-regulation-of-inflammasome-associated-pattern-recognition-receptors-and-the-relevance-to-disease-pathogenesis
#14
Virginie Deswaerte, Saleela M Ruwanpura, Brendan J Jenkins
Over the last decade it has emerged that inflammasome complexes provide a pivotal platform for the host innate immune system to respond to exogenous infectious microbes (viruses, bacteria, fungi) and non-infectious environmental agents (cigarette smoke, pollution), as well as endogenous "danger" signals. Upon the canonical activation of inflammasomes, a key effector function is to catalyze, via caspase-1, the maturation of the potent pro-inflammatory cytokines interleukin (IL)-1β and IL-18, which, in addition to chronic inflammatory responses have also been intimately linked to the inflammatory form of lytic cell death, pyroptosis...
September 30, 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27692897/optogenetic-immunomodulation-shedding-light-on-antitumor-immunity
#15
REVIEW
Peng Tan, Lian He, Gang Han, Yubin Zhou
Microbial opsin-based optogenetic tools have been transformative for neuroscience. To extend optogenetic approaches to the immune system to remotely control immune responses with superior spatiotemporal precision, pioneering tools have recently been crafted to modulate lymphocyte trafficking, inflammasome activation, dendritic cell (DC) maturation, and antitumor immunity through the photoactivation of engineered chemokine receptors and calcium release-activated calcium channels. We highlight herein some conceptual design strategies for installing light sensitivities into the immune signaling network and, in parallel, we propose potential solutions for in vivo optogenetic applications in living organisms with near-infrared light-responsive upconversion nanomaterials...
September 28, 2016: Trends in Biotechnology
https://www.readbyqxmd.com/read/27692612/k-efflux-independent-nlrp3-inflammasome-activation-by-small-molecules-targeting-mitochondria
#16
Christina J Groß, Ritu Mishra, Katharina S Schneider, Guillaume Médard, Jennifer Wettmarshausen, Daniela C Dittlein, Hexin Shi, Oliver Gorka, Paul-Albert Koenig, Stephan Fromm, Giovanni Magnani, Tamara Ćiković, Lara Hartjes, Joachim Smollich, Avril A B Robertson, Matthew A Cooper, Marc Schmidt-Supprian, Michael Schuster, Kate Schroder, Petr Broz, Claudia Traidl-Hoffmann, Bruce Beutler, Bernhard Kuster, Jürgen Ruland, Sabine Schneider, Fabiana Perocchi, Olaf Groß
Imiquimod is a small-molecule ligand of Toll-like receptor-7 (TLR7) that is licensed for the treatment of viral infections and cancers of the skin. Imiquimod has TLR7-independent activities that are mechanistically unexplained, including NLRP3 inflammasome activation in myeloid cells and apoptosis induction in cancer cells. We investigated the mechanism of inflammasome activation by imiquimod and the related molecule CL097 and determined that K(+) efflux was dispensable for NLRP3 activation by these compounds...
September 24, 2016: Immunity
https://www.readbyqxmd.com/read/27689324/enhancement-of-endothelial-permeability-by-free-fatty-acid-through-lysosomal-cathepsin-b-mediated-nlrp3-inflammasome-activation
#17
Lei Wang, Yang Chen, Xiang Li, Youzhi Zhang, Erich Gulbins, Yang Zhang
Obesity is an important risk factor for exacerbating chronic diseases such as cardiovascular disease and cancer. High serum level of saturated free fatty acids such as palmitate is an important contributor for obesity-induced diseases. Here, we examined the contribution of inflammasome activation in vascular cells to free fatty acid-induced endothelial dysfunction and vascular injury in obesity. Our findings demonstrated that high fat diet-induced impairment of vascular integrity and enhanced vascular permeability in the myocardium in mice were significantly attenuated by Nlrp3 gene deletion...
September 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/27665283/pterostilbene-attenuates-early-brain-injury-following-subarachnoid-hemorrhage-via-inhibition-of-the-nlrp3-inflammasome-and-nox2-related-oxidative-stress
#18
Haixiao Liu, Lei Zhao, Liang Yue, Bodong Wang, Xia Li, Hao Guo, Yihui Ma, Chen Yao, Li Gao, Jianping Deng, Lihong Li, Dayun Feng, Yan Qu
Pterostilbene (PTE), one of the polyphenols present in plants such as blueberries and grapes, has been suggested to have various effects, such as anti-oxidation, anti-apoptosis, and anti-cancer effects. Subarachnoid hemorrhage (SAH) is a severe neurological event known for its high morbidity and mortality. Recently, early brain injury (EBI) has been reported to play a significant role in the prognosis of patients with SAH. The present study aimed to investigate whether PTE could attenuate EBI after SAH was induced in C57BL/6 J mice...
September 24, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27662089/germline-nlrp1-mutations-cause-skin-inflammatory-and-cancer-susceptibility-syndromes-via-inflammasome-activation
#19
Franklin L Zhong, Ons Mamaï, Lorenzo Sborgi, Lobna Boussofara, Richard Hopkins, Kim Robinson, Ildikó Szeverényi, Takuya Takeichi, Reshmaa Balaji, Aristotle Lau, Hazel Tye, Keya Roy, Carine Bonnard, Patricia J Ahl, Leigh Ann Jones, Paul Baker, Lukas Lacina, Atsushi Otsuka, Pierre R Fournie, François Malecaze, E Birgitte Lane, Masashi Akiyama, Kenji Kabashima, John E Connolly, Seth L Masters, Vincent J Soler, Salma Samir Omar, John A McGrath, Roxana Nedelcu, Moez Gribaa, Mohamed Denguezli, Ali Saad, Sebastian Hiller, Bruno Reversade
Inflammasome complexes function as key innate immune effectors that trigger inflammation in response to pathogen- and danger-associated signals. Here, we report that germline mutations in the inflammasome sensor NLRP1 cause two overlapping skin disorders: multiple self-healing palmoplantar carcinoma (MSPC) and familial keratosis lichenoides chronica (FKLC). We find that NLRP1 is the most prominent inflammasome sensor in human skin, and all pathogenic NLRP1 mutations are gain-of-function alleles that predispose to inflammasome activation...
September 22, 2016: Cell
https://www.readbyqxmd.com/read/27650313/the-nlrp3-inflammasome-in-pathogenic-particle-and-fibre-associated-lung-inflammation-and-diseases
#20
REVIEW
Mutlay Sayan, Brooke T Mossman
The concept of the inflammasome, a macromolecular complex sensing cell stress or danger signals and initiating inflammation, was first introduced approximately a decade ago. Priming and activation of these intracellular protein platforms trigger the maturation of pro-inflammatory chemokines and cytokines, most notably, interleukin-1β (IL-1β) and IL-18, to promulgate innate immune defenses. Although classically studied in models of gout, Type II diabetes, Alzheimer's disease, and multiple sclerosis, the importance and mechanisms of action of inflammasome priming and activation have recently been elucidated in cells of the respiratory tract where they modulate the responses to a number of inhaled pathogenic particles and fibres...
20, 2016: Particle and Fibre Toxicology
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