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https://www.readbyqxmd.com/read/29216786/a-study-of-single-nucleotide-polymorphisms-in-cd157-aim2-and-jarid2-genes-in-han-chinese-children-with-autism-spectrum-disorder
#1
Weiming Mo, Jun Liu, Zengyu Zhang, Hong Yu, Aiping Yang, Fei Qu, Pingfang Hu, Zhuo Liu, Fengpei Hu
PURPOSE: Autism spectrum disorder (ASD) is a group of developmental brain disorders caused by genetic and environmental factors. The objective of this study was to investigate whether single nucleotide polymorphisms (SNPs) in genes related to immune function were associated with ASD in Chinese Han children. MATERIALS AND METHODS: A total of 201 children with ASD and 200 age- and gender-matched healthy controls were recruited from September 2012 to June 2106. A TaqMan probe-based approach was used to genotype SNPs corresponding to rs28532698 and rs4301112 in CD157, rs855867 in AIM2, and rs2237126 in JARID2...
December 7, 2017: Nordic Journal of Psychiatry
https://www.readbyqxmd.com/read/29203515/brucella-abortus-triggers-a-cgas-independent-sting-pathway-to-induce-host-protection-that-involves-guanylate-binding-proteins-and-inflammasome-activation
#2
Miriam M Costa Franco, Fernanda Marim, Erika S Guimarães, Natan R G Assis, Daiane M Cerqueira, Juliana Alves-Silva, Jerome Harms, Gary Splitter, Judith Smith, Thirumala-Devi Kanneganti, Nina M G P de Queiroz, Delia Gutman, Glen N Barber, Sergio C Oliveira
Immunity against microbes depends on recognition of pathogen-associated molecular patterns by innate receptors. Signaling pathways triggered by Brucella abortus DNA involves TLR9, AIM2, and stimulator of IFN genes (STING). In this study, we observed by microarray analysis that several type I IFN-associated genes, such as IFN-β and guanylate-binding proteins (GBPs), are downregulated in STING knockout (KO) macrophages infected with Brucella or transfected with DNA. Additionally, we determined that STING and cyclic GMP-AMP synthase (cGAS) are important to engage the type I IFN pathway, but only STING is required to induce IL-1β secretion, caspase-1 activation, and GBP2 and GBP3 expression...
December 4, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29193282/hot-water-extract-of-sanguisorba-officinalis-ameliorates-endotoxin-induced-septic-shock-by-inhibiting-inflammasome-activation
#3
Dong-Won Seo, Yong-Il Cho, Suna Gu, Da-Hee Kim, Young-Joo Yi, Sang-Myeong Lee
The inflammasome is a multiprotein signaling complex that mediates inflammatory innate immune responses through caspase 1 activation and subsequent IL-1β secretion. Nonetheless, its aberrant activation often leads to inflammatory diseases. Therefore, targeting the inflammasome holds promise for the treatment of inflammation-related diseases. Our study showed that a hot-water extract of Sanguisorba officinalis (HSO) effectively suppressed inflammasome activation triggered by ATP, nigericin, microbial pathogens, and dsDNA in bone marrow-derived macrophages (BMDMs)...
November 29, 2017: Microbiology and Immunology
https://www.readbyqxmd.com/read/29191979/shigella-hijacks-the-glomulin-ciaps-inflammasome-axis-to-promote-inflammation
#4
Shiho Suzuki, Toshihiko Suzuki, Hitomi Mimuro, Tsunehiro Mizushima, Chihiro Sasakawa
Shigella deploys a unique mechanism to manipulate macrophage pyroptosis by delivering the IpaH7.8 E3 ubiquitin ligase via its type III secretion system. IpaH7.8 ubiquitinates glomulin (GLMN) and elicits its degradation, thereby inducing inflammasome activation and pyroptotic cell death of macrophages. Here, we show that GLMN specifically binds cellular inhibitor of apoptosis proteins 1 and 2 (cIAP1 and cIAP2), members of the inhibitor of apoptosis (IAP) family of RING-E3 ligases, which results in reduced E3 ligase activity, and consequently inflammasome-mediated death of macrophages...
November 30, 2017: EMBO Reports
https://www.readbyqxmd.com/read/29183866/an-optimized-whole-blood-assay-measuring-expression-and-activity-of-nlrp3-nlrc4-and-aim2-inflammasomes
#5
Lev Grinstein, Hella Luksch, Felix Schulze, Avril A B Robertson, Matthew A Cooper, Angela Rösen-Wolff, Stefan Winkler
The proinflammatory protease caspase-1 plays pivotal roles in central pathways of innate immunity, thereby contributing to pathogen clearance. Beside its physiological role, dysregulated activity of caspase-1 is known to contribute to an increasing number of diseases. In this study we optimized and validated a low-volume human whole blood assay facilitating the measurement of caspase-1 activation and inflammasome-related gene expression upon stimulation of the NLRP3, NLRC4 or AIM2 inflammasome. Using the NLRP3 inflammasome specific inhibitor MCC950 we were able to measure the activity of canonical or alternative NLRP3 pathways, AIM2 and NLRC4 inflammasomes in whole blood...
November 25, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29178062/aim2-inflammasome-is-critical-for-dsdna-induced-il-1%C3%AE-secretion-in-human-dental-pulp-cells
#6
Shuheng Huang, Zhi Song, Qiting Huang, Lan Jiang, Lingling Chen, Runfu Wang, Zhengmei Lin
The AIM2 inflammasome pathway has been determined to play an important role in cellular immune defense against bacterial and viral infections; however, its function and regulatory mechanism in human dental pulp cells (HDPCs) during pulpitis remains poorly understood. In this study, we explored whether the AIM2 inflammasome pathway was activated in HDPCs in response to dsDNA and defined its role in regulating IL-1β secretion. We demonstrated that stimulation with IFN-γ and cytoplasmic DNA significantly activated the AIM2 inflammasome and increased IL-1β secretion in HDPCs...
November 27, 2017: Inflammation
https://www.readbyqxmd.com/read/29171506/inflammasomes-the-eye-and-anti-inflammasome-therapy
#7
REVIEW
P Yerramothu, A K Vijay, M D P Willcox
Inflammasomes, key molecular regulators that play an important role in inflammation, consist of a central protein, an adaptor protein ASC (apoptosis speck-like protein) and a caspase-1 protein. Upon activation, caspase-1 induces maturation of cytokines such as interleukin-1β (IL-1β) and interleukin-18 (IL-18). The release of these cytokines can result in inflammation. Inflammasomes are activated by a variety of factors and their activation involves complex signalling leading to resolution of infection, but can also contribute to the pathology of inflammatory, autoimmune, and infectious diseases...
November 24, 2017: Eye
https://www.readbyqxmd.com/read/29128729/recent-advances-in-inflammasome-biology
#8
REVIEW
David E Place, Thirumala-Devi Kanneganti
The inflammasome is a complex of proteins that through the activity of caspase-1 and the downstream substrates gasdermin D, IL-1β, and IL-18 execute an inflammatory form of cell death termed pyroptosis. Activation of this complex often involves the adaptor protein ASC and upstream sensors including NLRP1, NLRP3, NLRC4, AIM2, and pyrin, which are activated by different stimuli including infectious agents and changes in cell homeostasis. Here we discuss new regulatory mechanisms that have been identified for the canonical inflammasomes, the most recently identified NLRP9b inflammasome, and the new gasdermin family of proteins that mediate pyroptosis and other forms of regulated cell death...
November 9, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/29100888/caspase-1-is-an-apical-caspase-leading-to-caspase-3-cleavage-in-the-aim2-inflammasome-response-independent-of-caspase-8
#9
Vitaliya Sagulenko, Nazarii Vitak, Parimala Vajjhala, James E Vince, Katryn J Stacey
Canonical inflammasomes are multiprotein complexes that can activate both caspase-1 and caspase-8. Caspase-1 drives rapid lysis of cells by pyroptosis and maturation of IL-1β and IL-18. In caspase-1-deficient cells, inflammasome formation still leads to caspase-3 activation and slower apoptotic death, dependent on caspase-8 as an apical caspase. A role for caspase-8 directly upstream of caspase-1 has also been suggested, but here we show that caspase-8-deficient macrophages have no defect in AIM2 inflammasome-mediated caspase-1 activation, pyroptosis and IL-1β release...
October 31, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29051224/advanced-glycation-end-products-impair-nlrp3-inflammasome-mediated-innate-immune-responses-in-macrophages
#10
Seunghwan Son, Inhwa Hwang, Seung Hyeok Han, Jeon-Soo Shin, Ok Sarah Shin, Je-Wook Yu
Advanced glycation end products (AGEs) are adducts formed on proteins by glycation with reducing sugars, such as glucose, and tend to form and accumulate under hyperglycemic conditions. AGE accumulation alters protein function and has been implicated in the pathogenesis of many degenerative diseases such as diabetic complications. AGEs have also been shown to promote the production of pro-inflammatory cytokines, but the roles of AGEs in inflammasome signaling have not been explored in detail. Here, we present evidence that AGEs attenuate activation of the NLRP3 inflammasome in bone marrow-derived macrophages (BMDMs) as determined by caspase-1 processing and interleukin-1β production...
October 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29045388/inflammatory-memory-sensitizes-skin-epithelial-stem-cells-to-tissue-damage
#11
Shruti Naik, Samantha B Larsen, Nicholas C Gomez, Kirill Alaverdyan, Ataman Sendoel, Shaopeng Yuan, Lisa Polak, Anita Kulukian, Sophia Chai, Elaine Fuchs
The skin barrier is the body's first line of defence against environmental assaults, and is maintained by epithelial stem cells (EpSCs). Despite the vulnerability of EpSCs to inflammatory pressures, neither the primary response to inflammation nor its enduring consequences are well understood. Here we report a prolonged memory to acute inflammation that enables mouse EpSCs to hasten barrier restoration after subsequent tissue damage. This functional adaptation does not require skin-resident macrophages or T cells...
October 26, 2017: Nature
https://www.readbyqxmd.com/read/29033131/oxysterol-restraint-of-cholesterol-synthesis-prevents-aim2-inflammasome-activation
#12
Eric V Dang, Jeffrey G McDonald, David W Russell, Jason G Cyster
Type I interferon restrains interleukin-1β (IL-1β)-driven inflammation in macrophages by upregulating cholesterol-25-hydroxylase (Ch25h) and repressing SREBP transcription factors. However, the molecular links between lipid metabolism and IL-1β production remain obscure. Here, we demonstrate that production of 25-hydroxycholesterol (25-HC) by macrophages is required to prevent inflammasome activation by the DNA sensor protein absent in melanoma 2 (AIM2). We find that in response to bacterial infection or lipopolysaccharide (LPS) stimulation, macrophages upregulate Ch25h to maintain repression of SREBP2 activation and cholesterol synthesis...
November 16, 2017: Cell
https://www.readbyqxmd.com/read/29033128/the-dna-inflammasome-in-human-myeloid-cells-is-initiated-by-a-sting-cell-death-program-upstream-of-nlrp3
#13
Moritz M Gaidt, Thomas S Ebert, Dhruv Chauhan, Katharina Ramshorn, Francesca Pinci, Sarah Zuber, Fionan O'Duill, Jonathan L Schmid-Burgk, Florian Hoss, Raymund Buhmann, Georg Wittmann, Eicke Latz, Marion Subklewe, Veit Hornung
Detection of cytosolic DNA constitutes a central event in the context of numerous infectious and sterile inflammatory conditions. Recent studies have uncovered a bipartite mode of cytosolic DNA recognition, in which the cGAS-STING axis triggers antiviral immunity, whereas AIM2 triggers inflammasome activation. Here, we show that AIM2 is dispensable for DNA-mediated inflammasome activation in human myeloid cells. Instead, detection of cytosolic DNA by the cGAS-STING axis induces a cell death program initiating potassium efflux upstream of NLRP3...
November 16, 2017: Cell
https://www.readbyqxmd.com/read/29030458/a-noncanonical-function-of-cgamp-in-inflammasome-priming-and-activation
#14
Karen V Swanson, Robert D Junkins, Cathryn J Kurkjian, Elizabeth Holley-Guthrie, Avani A Pendse, Rachid El Morabiti, Alex Petrucelli, Glen N Barber, Chris A Benedict, Jenny P-Y Ting
Recognition of pathogen-associated molecular patterns and danger-associated molecular patterns by host cells is an important step in innate immune activation. The DNA sensor cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) binds to DNA and produces cGAMP, which in turn binds to stimulator of interferon genes (STING) to activate IFN-I. Here we show that cGAMP has a noncanonical function in inflammasome activation in human and mouse cells. Inflammasome activation requires two signals, both of which are activated by cGAMP...
October 13, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28976036/overexpression-of-nlrp3-nlrc4-and-aim2-inflammasomes-and-their-priming-associated-molecules-tlr2-tlr4-dectin-1-dectin-2-and-nf%C3%AE%C2%BAb-in-malassezia-folliculitis
#15
Ni Liang, Yan-Ping Yang, Wei Li, Ya-Yun Wu, Zi-Wei Zhang, Yun Luo, Yi-Ming Fan
The activation of NLRP3, NLRC4 and AIM2 inflammasomes is pivotal for innate immunity against some pathogenic fungi, but their role in the pathogenesis of Malassezia folliculitis (MF) remains unclear. The objective of the study was to determine the expression of 4 canonical inflammasomes (NLRP1, NLRP3, NLRC4 and AIM2) and their priming-associated molecules (TLR2, TLR4, Dectin-1, Dectin-2 and NFκB) in MF lesion. Expression of NLRP1, NLRP3, NLRC4, AIM2, caspase-1, IL-1β, TLR2, TLR4, Dectin-1, Dectin-2 and NFκB was detected by immunohistochemistry in skin lesion of 23 MF patients and normal skin of 12 healthy subjects...
October 4, 2017: Mycoses
https://www.readbyqxmd.com/read/28968459/ifn-%C3%AE-extends-the-immune-functions-of-guanylate-binding-proteins-to-inflammasome-independent-antibacterial-activities-during-francisella-novicida-infection
#16
Pierre Wallet, Sacha Benaoudia, Amandine Mosnier, Brice Lagrange, Amandine Martin, Helena Lindgren, Igor Golovliov, Fanny Michal, Pauline Basso, Sophia Djebali, Angelina Provost, Omran Allatif, Etienne Meunier, Petr Broz, Masahiro Yamamoto, Bénédicte F Py, Eric Faudry, Anders Sjöstedt, Thomas Henry
Guanylate binding proteins (GBPs) are interferon-inducible proteins involved in the cell-intrinsic immunity against numerous intracellular pathogens. The molecular mechanisms underlying the potent antibacterial activity of GBPs are still unclear. GBPs have been functionally linked to the NLRP3, the AIM2 and the caspase-11 inflammasomes. Two opposing models are currently proposed to explain the GBPs-inflammasome link: i) GBPs would target intracellular bacteria or bacteria-containing vacuoles to increase cytosolic PAMPs release ii) GBPs would directly facilitate inflammasome complex assembly...
October 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28963531/methylene-blue-inhibits-nlrp3-nlrc4-aim2-and-non-canonical-inflammasome-activation
#17
Huijeong Ahn, Seung Goo Kang, Sung-Il Yoon, Hyun-Jeong Ko, Pyeung-Hyeun Kim, Eui-Ju Hong, Beum-Soo An, Eunsong Lee, Geun-Shik Lee
Methylene blue (MB), which has antioxidant, anti-inflammatory, neuroprotective, and mitochondria protective effects, has been widely used as a dye and medication. However, the effect of MB on inflammasome activation has not yet been studied. Inflammasomes are multi-protein complexes that induce maturation of interleukins (ILs)-1β and -18 as well as caspase-1-mediated cell death, known as pyroptosis. Dysregulation of inflammasomes causes several diseases such as type 2 diabetes, Alzheimer's disease, and gout...
September 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28947539/priming-and-activation-of-inflammasome-by-canarypox-virus-vector-alvac-via-the-cgas-ifi16-sting-type-i-ifn-pathway-and-aim2-sensor
#18
Fengliang Liu, Qingli Niu, Xiuzhen Fan, Connie Liu, Jie Zhang, Zhi Wei, Wei Hou, Thirumala-Devi Kanneganti, Merlin L Robb, Jerome H Kim, Nelson L Michael, Jiaren Sun, Lynn Soong, Haitao Hu
Viral vectors derived from different virus families, including poxvirus (canarypox virus vector ALVAC) and adenovirus (human Ad5 vector), have been widely used in vaccine development for a range of human diseases including HIV/AIDS. Less is known about the mechanisms underlying the host innate response to these vectors. Increasing evidence from clinical vaccine trials testing different viral vectors has suggested the importance of understanding basic elements of host-viral vector interactions. In this study, we investigated the innate interactions of APCs with two commonly used HIV vaccine vectors, ALVAC and Ad5, and identified AIM2 as an innate sensor for ALVAC, triggering strong inflammasome activation in both human and mouse APCs...
November 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28935571/aggravated-postinfarct-heart-failure-in-type-2-diabetes-is-associated-with-impaired-mitophagy-and-exaggerated-inflammasome-activation
#19
Thota Durga Devi, Mohan Babu, Petri Mäkinen, Minna Kaikkonen, Merja Heinaniemi, Hanne Laakso, Elias Ylä-Herttuala, Lassi Rieppo, Timo Liimatainen, Nikolay Naumenko, Pasi Tavi, Seppo Ylä-Herttuala
Type 2 diabetes mellitus (T2DM) is a major risk factor for heart disease. Mortality rates after myocardial infarction (MI) are significantly increased in T2DM patients because of dysfunctional left ventricle (LV). However, molecular pathways underlying accelerated heart failure (HF) after MI in T2DM remain unclear. We investigated the underlying mechanisms by inducing MI in a well-established model of T2DM and control mice. Cardiac imaging revealed a significantly decreased global left ventricular ejection fraction in parallel with increased mortality after MI in T2DM mice compared with control mice...
September 19, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28928425/double-deficiency-of-trex2-and-dnase1l2-nucleases-leads-to-accumulation-of-dna-in-lingual-cornifying-keratinocytes-without-activating-inflammatory-responses
#20
Joan Manils, Heinz Fischer, Joan Climent, Eduard Casas, Celia García-Martínez, Jordi Bas, Supawadee Sukseree, Tanya Vavouri, Francisco Ciruela, Josep Maria de Anta, Erwin Tschachler, Leopold Eckhart, Concepció Soler
The cornification of keratinocytes on the surface of skin and oral epithelia is associated with the degradation of nuclear DNA. The endonuclease DNase1L2 and the exonuclease Trex2 are expressed specifically in cornifying keratinocytes. Deletion of DNase1L2 causes retention of nuclear DNA in the tongue epithelium but not in the skin. Here we report that lack of Trex2 results in the accumulation of DNA fragments in the cytoplasm of cornifying lingual keratinocytes and co-deletion of DNase1L2 and Trex2 causes massive accumulation of DNA fragments throughout the cornified layers of the tongue epithelium...
September 19, 2017: Scientific Reports
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