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https://www.readbyqxmd.com/read/27907115/brucella-melitensis-16m-regulates-the-effect-of-air-domain-on-inflammatory-factors-autophagy-and-apoptosis-in-mouse-macrophage-through-the-ros-signaling-pathway
#1
Tiansen Li, Yafang Xu, Laizhen Liu, Meiling Huang, Zhen Wang, Zhixia Tong, Hui Zhang, Fei Guo, Chuangfu Chen
Brucellosis is a highly contagious zoonosis caused by Brucella. Brucella can invade and persist inside host cells, which results in chronic infection. We constructed AIR interference and overexpression lentiviruses to acquire AIR interference, overexpression, and rescue stable expression cell lines. We also established a Brucella melitensis 16M-infected macrophage model, which was treated with either the vehicle control or NAC (ROS scavenger N-acetylcysteine (NAC) for 0, 3, 6, 12, and 24 h. Confocal laser microscopy, transmission electron microscopy, fluorescence quantitative PCR, flow cytometry, ELISA, and Western blot were used to detect inflammation, cell autophagy and apoptosis-related protein expression levels, ROS levels, and the distribution of mitochondria...
2016: PloS One
https://www.readbyqxmd.com/read/27852921/a-role-for-the-inflammasome-in-spontaneous-labor-at-term-with-acute-histologic-chorioamnionitis
#2
Nardhy Gomez-Lopez, Roberto Romero, Yi Xu, Olesya Plazyo, Ronald Unkel, Nandor Gabor Than, Piya Chaemsaithong, Tinnakorn Chaiworapongsa, Zhong Dong, Adi L Tarca, Vikki M Abrahams, Lami Yeo, Sonia S Hassan
Inflammasomes are cytosolic signaling platforms that regulate the activation of caspase (CASP)-1, which induces the maturation of interleukin (IL)-1β and IL-18. Herein, we determined whether the chorioamniotic membranes from women in spontaneous labor at term with acute histologic chorioamnionitis express major inflammasome components and whether these changes are associated with the activation of CASP-1 and CASP-4 and the release of mature IL-1β and IL-18. When comparing the chorioamniotic membranes from women in spontaneous labor at term with acute histologic chorioamnionitis to those without this placental lesion, we found that (1) the messenger RNA (mRNA) abundance of NLR family pyrin domain containing 3 (NLRP3), NLR family CARD domain containing 4 (NLRC4), absent in melanoma 2 (AIM2), and nucleotide binding oligomerization domain 2 (NOD2) was higher; (2) the NLRP3 and NLRC4 protein quantities were increased; (3) the mRNA and protein expressions of CASP-1 and its active forms were greater; (4) CASP-4 was increased at the mRNA level only; (5) the mRNA and protein expressions of IL-1β and its mature form were higher; and (6) a modest increase in the total protein concentration and abundance of the mature form of IL-18 was observed...
November 16, 2016: Reproductive Sciences
https://www.readbyqxmd.com/read/27846608/the-dna-sensing-aim2-inflammasome-controls-radiation-induced-cell-death-and-tissue-injury
#3
Bo Hu, Chengcheng Jin, Hua-Bing Li, Jiyu Tong, Xinshou Ouyang, Naniye Malli Cetinbas, Shu Zhu, Till Strowig, Fred C Lam, Chen Zhao, Jorge Henao-Mejia, Omer Yilmaz, Katherine A Fitzgerald, Stephanie C Eisenbarth, Eran Elinav, Richard A Flavell
Acute exposure to ionizing radiation induces massive cell death and severe damage to tissues containing actively proliferating cells, including bone marrow and the gastrointestinal tract. However, the cellular and molecular mechanisms underlying this pathology remain controversial. Here, we show that mice deficient in the double-stranded DNA sensor AIM2 are protected from both subtotal body irradiation-induced gastrointestinal syndrome and total body irradiation-induced hematopoietic failure. AIM2 mediates the caspase-1-dependent death of intestinal epithelial cells and bone marrow cells in response to double-strand DNA breaks caused by ionizing radiation and chemotherapeutic agents...
November 11, 2016: Science
https://www.readbyqxmd.com/read/27806943/hmgb1-induces-an-inflammatory-response-in-the-chorioamniotic-membranes-that-is-partially-mediated-by-the-inflammasome
#4
Olesya Plazyo, Roberto Romero, Ronald Unkel, Amapola Balancio, Tara N Mial, Yi Xu, Zhong Dong, Sonia S Hassan, Nardhy Gomez-Lopez
Spontaneous preterm labor occurs in two subsets of patients with sterile intra-amniotic inflammation, which is induced by alarmins such as high-mobility group box-1 (HMGB1). Inflammasomes are also implicated in the process of spontaneous preterm labor with acute chorioamnionitis. Therefore, we investigated whether HMGB1 initiates an inflammasome-associated inflammatory response in the chorioamniotic membranes. Incubation of the chorioamniotic membranes with HMGB1: 1) induced the release of mature IL-1beta and IL-6; 2) upregulated the mRNA expression of the pro-inflammatory mediators NFKB1, IL6, TNF, IL1A, IFNG, and HMGB1 receptors RAGE and TLR2; 3) upregulated the mRNA expression of the inflammasome components NLRP3 and AIM2, and NOD proteins (NOD1 and NOD2); 4) increased the protein concentrations of NLRP3 and NOD2; 5) increased the concentration of caspase-1 and the quantity of its active form (p20); and 6) upregulated the mRNA expression and active form of MMP-9...
November 2, 2016: Biology of Reproduction
https://www.readbyqxmd.com/read/27806724/a-network-pathway-based-module-identification-for-predicting-the-prognosis-of-ovarian-cancer-patients
#5
Xin Wang, Shan-Shan Wang, Lin Zhou, Li Yu, Lan-Mei Zhang
BACKGROUND: This study aimed to screen multiple genes biomarkers based on gene expression data for predicting the survival of ovarian cancer patients. METHODS: Two microarray data of ovarian cancer samples were collected from The Cancer Genome Atlas (TCGA) database. The data in the training set were used to construct Reactome functional interactions network, which then underwent Markov clustering, supervised principal components, Cox proportional hazard model to screen significantly prognosis related modules...
November 2, 2016: Journal of Ovarian Research
https://www.readbyqxmd.com/read/27800616/nlrp12-negatively-regulates-proinflammatory-cytokine-production-and-host-defense-against-brucella-abortus
#6
Tatiana N Silveira, Marco Túlio R Gomes, Luciana S Oliveira, Priscila C Campos, Gabriela G Machado, Sergio C Oliveira
Brucella abortus is the causative agent of brucellosis, which causes abortion in domestic animals and undulant fever in humans. This bacterium infects and proliferates mainly in macrophages and dendritic cells, where it is recognized by pattern recognition receptors (PRRs) including Nod-like receptors (NLRs). Our group recently demonstrated the role of AIM2 and NLRP3 in Brucella recognition. Here, we investigated the participation of NLRP12 in innate immune response to B. abortus. We show that NLRP12 inhibits the early production of IL-12 by bone marrow-derived macrophages upon B...
November 1, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27796369/pyk2-activates-the-nlrp3-inflammasome-by-directly-phosphorylating-asc-and-contributes-to-inflammasome-dependent-peritonitis
#7
I-Che Chung, Chun-Nan OuYang, Sheng-Ning Yuan, Hsin-Pai Li, Jeng-Ting Chen, Hui-Ru Shieh, Yu-Jen Chen, David M Ojcius, Ching-Liang Chu, Jau-Song Yu, Yu-Sun Chang, Lih-Chyang Chen
The inflammasome adaptor protein, ASC, contributes to both innate immune responses and inflammatory diseases via self-oligomerization, which leads to the activation of the protease, caspase-1. Here, we report that the cytosolic tyrosine kinases, FAK and Pyk2, are differentially involved in NLRP3 and AIM2 inflammasome activation. The inhibition of FAK and Pyk2 with RNA interference or chemical inhibitors dramatically abolished ASC oligomerization, caspase-1 activation, and IL-1β secretion in response to NLRP3 or AIM2 stimulation...
October 31, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27788256/p2y1-receptor-signaling-contributes-to-high-salt-induced-priming-of-the-nlrp3-inflammasome-in-retinal-pigment-epithelial-cells
#8
Philipp Prager, Margrit Hollborn, Anja Steffen, Peter Wiedemann, Leon Kohen, Andreas Bringmann
BACKGROUND: Systemic hypertension is a risk factor of age-related macular degeneration (AMD), a chronic inflammatory disease. Acute hypertension is caused by increased extracellular osmolarity after intake of dietary salt (NaCl). We determined in cultured human retinal pigment epithelial (RPE) cells whether high extracellular NaCl alters the gene expression of inflammasome-associated proteins, and whether autocrine/paracrine purinergic (P2) receptor signaling contributes to the NaCl-induced NLRP3 gene expression...
2016: PloS One
https://www.readbyqxmd.com/read/27779186/pkm2-dependent-glycolysis-promotes-nlrp3-and-aim2-inflammasome-activation
#9
Min Xie, Yan Yu, Rui Kang, Shan Zhu, Liangchun Yang, Ling Zeng, Xiaofang Sun, Minghua Yang, Timothy R Billiar, Haichao Wang, Lizhi Cao, Jianxin Jiang, Daolin Tang
Sepsis, severe sepsis and septic shock are the main cause of mortality in non-cardiac intensive care units. Immunometabolism has been linked to sepsis; however, the precise mechanism by which metabolic reprogramming regulates the inflammatory response is unclear. Here we show that aerobic glycolysis contributes to sepsis by modulating inflammasome activation in macrophages. PKM2-mediated glycolysis promotes inflammasome activation by modulating EIF2AK2 phosphorylation in macrophages. Pharmacological and genetic inhibition of PKM2 or EIF2AK2 attenuates NLRP3 and AIM2 inflammasomes activation, and consequently suppresses the release of IL-1β, IL-18 and HMGB1 by macrophages...
October 25, 2016: Nature Communications
https://www.readbyqxmd.com/read/27774630/redox-dependent-regulation-of-hepatocyte-aim2-inflammasome-activation-in-sterile-liver-injury-in-mice
#10
Qian Sun, Patricia Loughran, Richard Shapiro, Indira H Shrivastava, Daniel J Antoine, Tunliang Li, Zhengzheng Yan, Jie Fan, Timothy R Billiar, Melanie J Scott
: Sterile liver inflammation, such as liver ischemia reperfusion, hemorrhagic shock after trauma and drug-induced liver injury is initiated and regulated by endogenous mediators including DNA and reactive oxygen species. Here we identify a novel mechanism for redox-mediated regulation of AIM2-inflammasome activation in hepatocytes after redox stress in mice, which occurs via interaction with cytosolic HMGB1. We show that in liver during hemorrhagic shock in mice, and in hepatocytes after hypoxia with reoxygenation, cytosolic HMGB1 associates with AIM2 and is required for activation of caspase-1 in response to cytosolic DNA...
October 24, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27768771/silencing-of-asc-in-cutaneous-squamous-cell-carcinoma
#11
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/27753033/multiple-ways-of-cfdna-reception-and-following-ros-production-in-endothelial-cells
#12
Anna Yu Alekseeva, Larisa V Kameneva, Svetlana V Kostyuk, Natalia N Veiko
Oxidized cell-free DNA acts as a stress signal molecule and triggers an adaptive response in human cells. Various membrane DNA recognizing receptors are known as potential sensors for such DNA fragments. In order to clarify which of these sensors are able to interact with cfDNA fragments, circulating in human blood flow in heath and disease, we studied the influence of various cfDNA types on endothelial cells. We incubated these fragments at a physiologically optimal concentration with HUVEC cells for 3-24 h and detected the expression of either TLR9 or AIM2, RIG1 and STING receptors at mRNA and protein levels...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27751656/molecular-requirements-for-sensing-of-intracellular-microbial-nucleic-acids-by-the-innate-immune-system
#13
Stefanie Luecke, Søren R Paludan
Nucleic acids sensors of the innate immune system recognize various RNA and DNA structures during infection to induce transcription of interferon and pro-inflammatory cytokines and activation of inflammasomes. Cytosolic RNA is recognized by RIG-I and MDA5, while intracellular DNA is sensed among others by cGAS, AIM2, IFI16 and RNA polymerase III. The diversity of nucleic acid species produced during infection in the cytosol and nucleus and the limited chemical differences between self and non-self nucleic acids challenge the host's innate pattern recognition system to ensure reliable sensing while avoiding immune activation by self nucleic acids...
October 14, 2016: Cytokine
https://www.readbyqxmd.com/read/27728782/irgb10-exposes-bacteria-s-intimate-secrets
#14
Florian Hoss, Christina F Budden, Eicke Latz
When bacteria infect a cell, the bacterial membrane partially shields microbial structures from the immune system, preventing detection and clearance. In a recent issue of Cell, Man et al. (2016) show that the interferon-inducible protein IRGB10 liberates bacterial ligands for sensing by both the AIM2 and the non-canonical NLRP3 inflammasomes.
October 10, 2016: Developmental Cell
https://www.readbyqxmd.com/read/27699580/inflammasomes-and-its-importance-in-viral-infections
#15
Gaurav Shrivastava, Moisés León-Juárez, Julio García-Cordero, David Eduardo Meza-Sánchez, Leticia Cedillo-Barrón
A complex interplay between pathogen and host determines the immune response during viral infection. A set of cytosolic sensors are expressed by immune cells to detect viral infection. NOD-like receptors (NLRs) comprise a large family of intracellular pattern recognition receptors. Members of the NLR family assemble into large multiprotein complexes, termed inflammasomes, which induce downstream immune responses to specific pathogens, environmental stimuli, and host cell damage. Inflammasomes are composed of cytoplasmic sensor molecules such as NLRP3 or absent in melanoma 2 (AIM2), the adaptor protein ASC (apoptosis-associated speck-like protein containing caspase recruitment domain), and the effector protein procaspase-1...
October 3, 2016: Immunologic Research
https://www.readbyqxmd.com/read/27693356/irgb10-liberates-bacterial-ligands-for-sensing-by-the-aim2-and-caspase-11-nlrp3-inflammasomes
#16
Si Ming Man, Rajendra Karki, Miwa Sasai, David E Place, Sannula Kesavardhana, Jamshid Temirov, Sharon Frase, Qifan Zhu, R K Subbarao Malireddi, Teneema Kuriakose, Jennifer L Peters, Geoffrey Neale, Scott A Brown, Masahiro Yamamoto, Thirumala-Devi Kanneganti
The inflammasome is an intracellular signaling complex, which on recognition of pathogens and physiological aberration, drives activation of caspase-1, pyroptosis, and the release of the pro-inflammatory cytokines IL-1β and IL-18. Bacterial ligands must secure entry into the cytoplasm to activate inflammasomes; however, the mechanisms by which concealed ligands are liberated in the cytoplasm have remained unclear. Here, we showed that the interferon-inducible protein IRGB10 is essential for activation of the DNA-sensing AIM2 inflammasome by Francisella novicida and contributed to the activation of the LPS-sensing caspase-11 and NLRP3 inflammasome by Gram-negative bacteria...
October 6, 2016: Cell
https://www.readbyqxmd.com/read/27657699/correction-shikonin-suppresses-nlrp3-and-aim2-inflammasomes-by-direct-inhibition-of-caspase-1
#17
Jernej Zorman, Petra Sušjan, Iva Hafner-Bratkovič
[This corrects the article DOI: 10.1371/journal.pone.0159826.].
2016: PloS One
https://www.readbyqxmd.com/read/27636895/immune-complexed-adenovirus-induce-aim2-mediated-pyroptosis-in-human-dendritic-cells
#18
Karsten Eichholz, Thierry Bru, Thi Thu Phuong Tran, Paulo Fernandes, Hugh Welles, Franck J D Mennechet, Nicolas Manel, Paula Alves, Matthieu Perreau, Eric J Kremer
Human adenoviruses (HAdVs) are nonenveloped proteinaceous particles containing a linear double-stranded DNA genome. HAdVs cause a spectrum of pathologies in all populations regardless of health standards. Following repeat exposure to multiple HAdV types, we develop robust and long-lived humoral and cellular immune responses that provide life-long protection from de novo infections and persistent HAdV. How HAdVs, anti-HAdV antibodies and antigen presenting cells (APCs) interact to influence infection is still incompletely understood...
September 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27561456/aim-2-inflammasomes-regulate-neuronal-morphology-and-influence-anxiety-and-memory-in-mice
#19
Pei-Jung Wu, Hsin-Yu Liu, Tzyy-Nan Huang, Yi-Ping Hsueh
Inflammasomes are the protein assemblies that consist of inflammasome sensors, adaptor apoptosis-associated speck-like proteins containing a CARD (ASC) and inflammasome caspase. Inflammasomes sense multiple danger signals via various inflammasome sensors and consequently use caspase to trigger proteolytic processing and secretion of IL-1β cytokines. Recent studies have suggested that neurons use their own innate immune system to detect danger signals and regulate neuronal morphology. Here, we investigate whether inflammasomes, the critical components of innate immunity, participate in regulation of neuronal morphology and function...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27525422/the-influence-of-radiotherapy-on-aim2-inflammasome-in-radiation-pneumonitis
#20
Qianyu Zhang, Qinyong Hu, Yuxin Chu, Bin Xu, Qibin Song
This study aims to investigate the influence of radiotherapy on absent in melanoma 2 (AIM2) inflammasome in radiation pneumonitis (RP). A rat model of RP was established. H&E staining was used to test radiation-induced lung tissue injury. Immunohistochemistry (IHC) was used to detect the expression of AIM2 and IL-1β in rat lung tissues. Milliplex assay was used to test cytokine levels in rat serum. Comet assay was adopted to examine DNA breaks in THP1 cells. RT-PCR was used to detect the messenger RNA (mRNA) expression of AIM2, caspase-1, and IL-1β in THP1 cells...
October 2016: Inflammation
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