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https://www.readbyqxmd.com/read/28813641/aim2-inflammasome-activation-and-regulation-a-structural-perspective
#1
Bing Wang, Qian Yin
Absent in melanoma 2 (AIM2) inflammasome is a multi-protein platform that recognizes aberrant cytoplasmic dsDNA and induces cytokine maturation, release and pyroptosis. It is composed of AIM2, apoptosis-associated speck-like protein containing a CARD (ASC), and caspase-1. Recent X-ray crystallographic and high resolution cryo-electron microscopic (cryo-EM) studies have revealed a series of structures in AIM2 inflammasome activation and regulation. One prominent feature common in multiple steps is the assembly of high-order structures, especially helical filaments nucleated by upstream molecules, rather than stoichiometric complexes...
August 13, 2017: Journal of Structural Biology
https://www.readbyqxmd.com/read/28809949/maturation-dependent-expression-of-aim2-in-human-b-cells
#2
Alexandra Svensson, Marianela Patzi Churqui, Kerstin Schlüter, Liza Lind, Kristina Eriksson
Intracellular DNA- and RNA-sensing receptors, such as the IFN-inducible protein Absent in Melanoma 2 (AIM2), serve as host sensors against a wide range of infections. Immune sensing and inflammasome activation by AIM2 has been implicated in innate antiviral recognition in many experimental systems using cell-lines and animal models. However, little is known about the expression and function of AIM2 in freshly isolated human cells. In this study we investigated the expression of AIM2 in different cell types derived from human cord and adult peripheral blood, in steady state and following in vitro-activation...
2017: PloS One
https://www.readbyqxmd.com/read/28802238/expression-and-clinical-significance-of-absent-in-melanoma-2-in-colorectal-cancer
#3
Zhi Zhang, Xiaoqiang Dong, Xiaodong Yang, Daiwei Wan, Liang Sun, Mengmeng Gu, Ming Li, Zheng Zhu, Jin Wang, Zengfu Shang, Songbing He
Increasing research has indicated that absent in melanoma 2 (AIM2) is aberrantly expressed in several tumor types. However, the association between AIM2 expression and clinicopathological factors or prognosis of patient with colorectal cancer (CRC) remains elusive. In the present study, we first examined the protein and mRNA expression of AIM2 in CRC cell lines by western blotting and quantitative RT-PCR (qRT-PCR). Then, we detected AIM2 expression in CRC tissue using western blotting and immunohistochemistry (IHC) respectively to evaluate its clinicopathological characteristics and prognosis in CRC...
August 9, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28790368/signs-of-innate-immune-activation-and-premature-immunosenescence-in-psoriasis-patients
#4
Liisi Šahmatova, Elena Sügis, Marina Šunina, Helen Hermann, Ele Prans, Maire Pihlap, Kristi Abram, Ana Rebane, Hedi Peterson, Pärt Peterson, Külli Kingo, Kai Kisand
Psoriasis is a chronic inflammatory disease that affects skin and is associated with systemic inflammation and many serious comorbidities ranging from metabolic syndrome to cancer. Important discoveries about psoriasis pathogenesis have enabled the development of effective biological treatments blocking the T helper 17 pathway. However, it has not been settled whether psoriasis is a T cell-mediated autoimmune disease or an autoinflammatory disorder that is driven by exaggerated innate immune signalling. Our comparative gene expression and hierarchical cluster analysis reveal important gene circuits involving innate receptors...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28746866/aim2-engages-active-but-unprocessed-caspase-1-to-induce-noncanonical-activation-of-the-nlrp3-inflammasome
#5
Larissa D Cunha, Alexandre L N Silva, Juliana M Ribeiro, Danielle P A Mascarenhas, Gustavo F S Quirino, Leonardo L Santos, Richard A Flavell, Dario S Zamboni
Inflammasomes are multimeric protein complexes that initiate inflammatory cascades. Their activation is a hallmark of many infectious or inflammatory diseases. Their composition and activity are specified by proinflammatory stimuli. For example, the NLRP3 inflammasome is activated in response to cell damage and K(+) efflux, whereas the AIM2 inflammasome is activated in response to cytosolic DNA. We used Legionella pneumophila, an intracellular bacterial pathogen that activates multiple inflammasomes, to elucidate the molecular mechanisms regulating inflammasome activation during infection...
July 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28724943/aim2-inflammasome-mediated-pyroptosis-in-enterovirus-a71-infected-neuronal-cells-restricts-viral-replication
#6
Thinesshwary Yogarajah, Kien Chai Ong, David Perera, Kum Thong Wong
Encephalomyelitis is a well-known complication of hand, foot, and mouth disease (HFMD) due to Enterovirus 71 (EV71) infection. Viral RNA/antigens could be detected in the central nervous system (CNS) neurons in fatal encephalomyelitis but the mechanisms of neuronal cell death is not clearly understood. We investigated the role of absent in melanoma 2 (AIM2) inflammasome in neuronal cell death, and its relationship to viral replication. Our transcriptomic analysis, RT-qPCR, Western blot, immunofluorescence and flow cytometry studies consistently showed AIM2 gene up-regulation and protein expression in EV-A71-infected SK-N-SH cells...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28683296/inflammasomes-on-the-crossroads-of-innate-immune-recognition-and-metabolic-control
#7
REVIEW
Tomasz Próchnicki, Eicke Latz
Inflammasomes are protein complexes formed upon encounter of microbial or damage-associated stimuli. The main output of inflammasome assembly is activation of caspase-1, a protease involved in both pro-inflammatory and host-protective responses. Defined bacterial or viral ligands have been identified for the inflammasome-forming receptors AIM2, NLRP1, and NLRC4. The signals activating other inflammasomes, NLRP3, NLRP6, and pyrin, are less well understood. Recent studies implicated several low-molecular-weight compounds traditionally linked to metabolism, not immunity, in modulation of inflammasome signaling...
July 5, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28679751/aim2-like-receptors-positively-and-negatively-regulate-the-interferon-response-induced-by-cytosolic-dna
#8
Yuki Nakaya, Jingtao Lilue, Spyridon Stavrou, Eileen A Moran, Susan R Ross
Cytosolic DNAs derived from retrotransposons serve as pathogen-associated molecular patterns for pattern recognition receptors (PRRs) that stimulate the induction of interferons (IFNs) and other cytokines, leading to autoimmune disease. Cyclic GMP-AMP synthase is one PRR that senses retrotransposon DNA, activating type I IFN responses through the stimulator of IFN genes (STING). Absent in melanoma 2 (AIM2)-like receptors (ALRs) have also been implicated in these pathways. Here we show that the mouse ALR IFI205 senses cytosolic retrotransposon DNA independently of cyclic GMP-AMP production...
July 5, 2017: MBio
https://www.readbyqxmd.com/read/28663562/expression-analysis-of-inflammasome-sensors-and-implication-of-nlrp12-inflammasome-in-prostate-cancer
#9
Dev Karan, Ossama Tawfik, Seema Dubey
Inflammasomes are multi-proteins complex regulating inflammation-associated signaling. While inflammation plays a critical role in cancer cell growth, studies remain uncharacterized on the role of inflammasomes in prostate cancer. Using Gene Expression Omnibus (GEO) public datasets, we screened the expression profiles of inflammasome sensors NLRP3, NLRC4, NLRP6, NRLP12, and AIM2 in prostate tumor tissues, and verified their mRNA level in a panel of prostate cancer cell lines. The selected expression of NLRP3 and NLRP12 inflammasomes was validated, and the clinical association was evaluated in human prostate archival tumor tissues...
June 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28642849/aim2-co-immunization-with-vp1-is-associated-with-increased-memory-cd8-t-cells-and-mounts-long-lasting-protection-against-coxsackievirus-b3-challenge
#10
Liang Yin, Dafei Chai, Yan Yue, Chunsheng Dong, Sidong Xiong
The recurrent Coxsackievirus B3 (CVB3) infection is the most important cause of intractable myocarditis which often leads to chronic myocarditis and even dilated cardiomyopathy. Therefore, enhanced DNA vaccines capable of memory CD8 T cells are essential for long-lasting immunological protection against CVB3 infection. In this study, absent in melanoma 2 (AIM2) was used as an adjuvant to enhance the induction of memory CD8 T cells elicited by VP1 (viral capsid protein 1) vaccine. Mice were intramuscularly injected with 50 μg AIM2 plasmid and equal amount of VP1 plasmid (pAIM2/pVP1) vaccine 4 times at 2 week-intervals...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28621333/francisella-requires-dynamic-type-vi-secretion-system-and-clpb-to-deliver-effectors-for-phagosomal-escape
#11
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/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
#12
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/28580773/hbx-mediated-decrease-of-aim2-contributes-to-hepatocellular-carcinoma-metastasis
#13
Shi-Lu Chen, Li-Li Liu, Shi-Xun Lu, Rong-Zhen Luo, Chun-Hua Wang, Hong Wang, Shao-Hang Cai, Xia Yang, Dan Xie, Chris Zhiyi Zhang, Jing-Ping Yun
Tumor metastasis is responsible for the high mortality rates in patients with hepatocellular carcinoma (HCC). Absent in Melanoma 2 (AIM2) has been implicated in inflammation and carcinogenesis, but its role in HCC metastasis remains unknown. Here, we show that AIM2 protein expression was noticeably reduced in HCC cell lines and clinical samples. A reduction in AIM2 was closely associated with higher serum AFP levels, vascular invasion, poor tumor differentiation, an incomplete tumor capsule and unfavorable postsurgical survival odds...
June 5, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28526809/tumor-cell-specific-aim2-regulates-growth-and-invasion-of-cutaneous-squamous-cell-carcinoma
#14
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...
July 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28524163/an-evolving-function-of-dna-containing-exosomes-in-chemotherapy-induced-immune-response
#15
Paul Kurywchak, Raghu Kalluri
Chemotherapy is a predominant strategy to treat cancer and is often associated with toxicities like severe diarrhea that puts patients at additional risk and can hinder treatment strategies. Lian et al. recently explored the immune-mediated mechanisms of Irinotecan-induced diarrhea in colorectal cancer and found that double-stranded DNA in small vesicles can launch inflammation pathways in immune cells through the cytosolic DNA sensor AIM2.
June 2017: Cell Research
https://www.readbyqxmd.com/read/28516116/asc-particle-induced-peritonitis
#16
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/28480966/human-cytomegalovirus-triggers-the-assembly-of-aim2-inflammasome-in-thp-1-derived-macrophages
#17
Yuan Huang, Lingling Liu, Di Ma, Yi Liao, Yuanyuan Lu, Heyu Huang, Wenqing Qin, Xinglou Liu, Feng Fang
Absent in melanoma 2 (AIM2) inflammasome is a multiprotein complex which plays a pivotal role in the host immune response to multiple pathogens. The role of AIM2 in human cytomegalovirus (HCMV) infection is poorly studied. Thus, using a small inference RNA (siRNA) approach and THP-1 derived macrophage cells infected with HCMV AD169 strain, we investigated the impact of HCMV infection on AIM2-mediated molecular events. Compared to wild-type cells, AIM2-defiecient macrophages showed a limited ability to activate caspase-1, process IL-1β, and induce cell death...
May 8, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28465544/lentinan-from-shiitake-selectively-attenuates-aim2-and-non-canonical-inflammasome-activation-while-inducing-pro-inflammatory-cytokine-production
#18
Huijeong Ahn, Eunsaem Jeon, Jin-Chul Kim, Seung Goo Kang, Sung-Il Yoon, Hyun-Jeong Ko, Pyeung-Hyeun Kim, Geun-Shik Lee
Lentinan extracted from shiitake (Lentinula edodes) is a β-glucan that has been reported as an intravenous anti-tumor polysaccharide via enhancement of the host immune system. In this study, we determined the effect of lentinan on inflammasome activation, a multi-protein platform, in myeloid cells. Mouse bone marrow-derived macrophages were treated with lentinan with/without inflammasome triggers, and maturation of interleukin (IL)-1β, IL-18, or caspase-1 was measured as a readout of inflammasome activation...
May 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28463821/mitochondrial-ros-induced-by-chronic-ethanol-exposure-promote-hyper-activation-of-the-nlrp3-inflammasome
#19
Laura R Hoyt, Matthew J Randall, Jennifer L Ather, Daniel P DePuccio, Christopher C Landry, Xi Qian, Yvonne M Janssen-Heininger, Albert van der Vliet, Anne E Dixon, Eyal Amiel, Matthew E Poynter
Alcohol use disorders are common both in the United States and globally, and are associated with a variety of co-morbid, inflammation-linked diseases. The pathogenesis of many of these ailments are driven by the activation of the NLRP3 inflammasome, a multi-protein intracellular pattern recognition receptor complex that facilitates the cleavage and secretion of the pro-inflammatory cytokines IL-1β and IL-18. We hypothesized that protracted exposure of leukocytes to ethanol would amplify inflammasome activation, which would help to implicate mechanisms involved in diseases associated with both alcoholism and aberrant NLRP3 inflammasome activation...
August 2017: Redox Biology
https://www.readbyqxmd.com/read/28424239/aim2-inflammasome-is-critical-for-influenza-induced-lung-injury-and-mortality
#20
Hongbo Zhang, Jiadi Luo, John F Alcorn, Kong Chen, Songqing Fan, Joseph Pilewski, Aizhong Liu, Wei Chen, Jay K Kolls, Jieru Wang
The absent in melanoma 2 (AIM2) inflammasome plays an important role in many viral and bacterial infections, but very little is known about its role in RNA virus infection, including influenza A virus (IAV). In this study, we have designed in vivo and in vitro studies to determine the role of AIM2 in infections with lethal doses of IAVs A/PR8/34 and A/California/07/09. In wild-type mice, IAV infection enhanced AIM2 expression, induced dsDNA release, and stimulated caspase-1 activation and release of cleaved IL-1β in the lung, which was significantly reduced in AIM2-deficient mice...
June 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
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