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https://www.readbyqxmd.com/read/29675024/activation-of-the-absent-in-melanoma-2-inflammasome-in-peripheral-blood-mononuclear-cells-from-idiopathic-pulmonary-fibrosis-patients-leads-to-the-release-of-pro-fibrotic-mediators
#1
Michela Terlizzi, Antonio Molino, Chiara Colarusso, Chantal Donovan, Pasquale Imitazione, Pasquale Somma, Rita P Aquino, Philip M Hansbro, Aldo Pinto, Rosalinda Sorrentino
Idiopathic pulmonary fibrosis (IPF) is a chronic fibro-proliferative disease characterized by poor prognosis, with a mean survival of ~2-3 years after definite diagnosis. The cause of IPF is still unknown but it is a heterogeneous condition in which the aberrant deposition of extracellular matrix leads to extensive lung remodeling. This remodeling is a consequence of inflammatory responses, but the mechanisms involved are poorly understood. In this study, we first analyzed a bleomycin-induced mouse model, which showed that higher expression of IL-1β, but not IL-18, was correlated to pulmonary cell infiltration and fibrosis...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29672590/hiv-replication-is-associated-to-inflammasomes-activation-il-1%C3%AE-il-18-and-caspase-1-expression-in-galt-and-peripheral-blood
#2
Manuel Gerónimo Feria, Natalia Andrea Taborda, Juan C Hernandez, Maria Teresa Rugeles
BACKGROUND: Human immunodeficiency virus (HIV) promotes an inflammatory process, leading to the progressive loss of the functional capacity of the immune system. The HIV infection induces alterations in several tissues, but mainly in the gut-associated lymphoid tissue (GALT). However, the degree of GALT deterioration varies among infected individuals. In fact, it has been shown that HIV-controllers, who spontaneously control viral replication, exhibit a lower inflammatory response, and a relative normal frequency and function of most of the immune cells...
2018: PloS One
https://www.readbyqxmd.com/read/29617808/novel-aspects-of-the-assembly-and-activation-of-inflammasomes-with-focus-on-the-nlrc4-inflammasome
#3
William G Fusco, Joseph A Duncan
Inflammasomes are multiprotein structures that activate caspase-1, support secretion of pro-inflammatory cytokines, IL-1β and IL-18, and also induce inflammatory programmed cell death, termed pyoptosis. Inflammasomes are activated in response to the detection of endogenous and microbially derived danger signals and are mediated by several classes of inflammasome-forming sensors. These include several nucleotide-binding proteins of the NOD-like receptor (NLR) family, including NLRP1, NLRP3 and NLRC4, as well as the proteins Absent in Melanoma 2 (AIM2) and Pyrin...
February 14, 2018: International Immunology
https://www.readbyqxmd.com/read/29594175/multiple-inflammasomes-may-regulate-the-interleukin-1-driven-inflammation-in-protracted-bacterial-bronchitis
#4
Alice C-H Chen, Hai B Tran, Yang Xi, Stephanie T Yerkovich, Katherine J Baines, Susan J Pizzutto, Melanie Carroll, Avril A B Robertson, Matthew A Cooper, Kate Schroder, Jodie L Simpson, Peter G Gibson, Greg Hodge, Ian B Masters, Helen M Buntain, Helen L Petsky, Samantha J Prime, Anne B Chang, Sandra Hodge, John W Upham
Protracted bacterial bronchitis (PBB) in young children is characterised by prolonged wet cough, prominent airway interleukin (IL)-1β expression and infection, often with nontypeable Haemophilus influenzae (NTHi). The mechanisms responsible for IL-1-driven inflammation in PBB are poorly understood. We hypothesised that the inflammation in PBB involves the NLRP3 and/or AIM2 inflammasome/IL-1β axis. Lung macrophages obtained from bronchoalveolar lavage (BAL), peripheral blood mononuclear cells (PBMCs), blood monocytes and monocyte-derived macrophages from patients with PBB and age-matched healthy controls were cultured in control medium or exposed to live NTHi...
January 2018: ERJ Open Research
https://www.readbyqxmd.com/read/29576797/inhibitory-effect-and-mechanism-of-arctium-lappa-extract-on-nlrp3-inflammasome-activation
#5
Young-Kyu Kim, Sushruta Koppula, Do-Wan Shim, Eun-Jung In, Su-Bin Kwak, Myong-Ki Kim, Sang-Hyeun Yu, Kwang-Ho Lee, Tae-Bong Kang
Arctium lappa (A. lappa) , Compositae, is considered a potential source of nutrition and is used as a traditional medicine in East Asian countries for centuries. Although several studies have shown its biological activities as an anti-inflammatory agent, there have been no reports on A. lappa with regard to regulatory role in inflammasome activation. The purpose of this study was to investigate the inhibitory effects of A. lappa extract (ALE) on NLRP3 inflammasome activation and explore the underlying mechanisms...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29576451/irf8-regulates-transcription-of-naips-for-nlrc4-inflammasome-activation
#6
Rajendra Karki, Ein Lee, David Place, Parimal Samir, Jayadev Mavuluri, Bhesh Raj Sharma, Arjun Balakrishnan, R K Subbarao Malireddi, Rechel Geiger, Qifan Zhu, Geoffrey Neale, Thirumala-Devi Kanneganti
Inflammasome activation is critical for host defenses against various microbial infections. Activation of the NLRC4 inflammasome requires detection of flagellin or type III secretion system (T3SS) components by NLR family apoptosis inhibitory proteins (NAIPs); yet how this pathway is regulated is unknown. Here, we found that interferon regulatory factor 8 (IRF8) is required for optimal activation of the NLRC4 inflammasome in bone-marrow-derived macrophages infected with Salmonella Typhimurium, Burkholderia thailandensis, or Pseudomonas aeruginosa but is dispensable for activation of the canonical and non-canonical NLRP3, AIM2, and Pyrin inflammasomes...
March 16, 2018: Cell
https://www.readbyqxmd.com/read/29575052/expression-profile-of-pattern-recognition-receptors-in-skeletal-muscle-of-sod1-g93a-als-mice-and-sporadic-als-patients
#7
Sonja Lehmann, Eliza Esch, Philipp Hartmann, Anand Goswami, Stefan Nikolin, Joachim Weis, Cordian Beyer, Sonja Johann
AIMS: Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of motoneurons and progressive muscle wasting. Inflammatory processes, mediated by non-neuronal cells, such as glial cells, are known to contribute to disease progression. Inflammasomes consist of pattern recognition receptors (PPRs), ASC and caspase 1 and are essential for interleukin (IL) processing and a rapid immune response after tissue damage. Recently, we described inflammasome activation in the spinal cord of ALS patients and in SOD1(G93A) ALS mice...
March 25, 2018: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/29562174/detrimental-type-i-interferon-signaling-dominates-protective-aim2-inflammasome-responses-during-francisella-novicida-infection
#8
Qifan Zhu, Si Ming Man, Rajendra Karki, R K Subbarao Malireddi, Thirumala-Devi Kanneganti
Interferons (IFNs) and inflammasomes are essential mediators of anti-microbial immunity. Type I IFN signaling drives activation of the AIM2 inflammasome in macrophages; however, the relative contribution of IFNs and inflammasome responses in host defense is less understood. We report intact AIM2 inflammasome responses in mice lacking type I IFN signaling during infection with F. novicida. Lack of type I IFN signaling conferred protection to F. novicida infection in contrast to the increased susceptibility in AIM2-deficient mice...
March 20, 2018: Cell Reports
https://www.readbyqxmd.com/read/29551295/systemic-activation-of-nlrp3-inflammasome-in-patients-with-severe-primary-sj%C3%A3-gren-s-syndrome-fueled-by-inflammagenic-dna-accumulations
#9
Aigli G Vakrakou, Sorina Boiu, Panayiotis D Ziakas, Evangelia Xingi, Haralabia Boleti, Menelaos N Manoussakis
Sjögren's syndrome (SS) patients manifest high cell-free DNA (cf-DNA) levels in serum, associated with impaired DNaseI activity. Undegraded DNA may accumulate in tissues and act as an inflammasome-activating signal. Herein, we investigated the occurrence of aberrant DNA build-up in various biologic compartments of SS patients and its correlation with the activity of NLRP3 and AIM2 inflammasomes. For this purpose, we evaluated sera, PBMC, circulating monocytes and salivary glands (SG) from different SS patient subgroups and controls...
March 15, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29549176/curcumin-suppresses-il-1%C3%AE-secretion-and-prevents-inflammation-through-inhibition-of-the-nlrp3-inflammasome
#10
Haipeng Yin, Qiang Guo, Xin Li, Tiantian Tang, Cuiling Li, Hengxiao Wang, Yuanxin Sun, Qi Feng, Chunhong Ma, Chengjiang Gao, Fan Yi, Jun Peng
Turmeric is traditionally used as a spice and coloring in foods. Curcumin is the primary active ingredient in the turmeric, and compelling evidence has shown that it has the ability to inhibit inflammation. However, the mechanism mediating its anti-inflammatory effects are not fully understood. We report that curcumin inhibited caspase-1 activation and IL-1β secretion through suppressing LPS priming and the inflammasome activation pathway in mouse bone marrow-derived macrophages. The inhibitory effect of curcumin on inflammasome activation was specific to the NLRP3, not to the NLRC4 or the AIM2 inflammasomes...
March 16, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29531021/tranilast-directly-targets-nlrp3-to-treat-inflammasome-driven-diseases
#11
Yi Huang, Hua Jiang, Yun Chen, Xiaqiong Wang, Yanqing Yang, Jinhui Tao, Xianming Deng, Gaolin Liang, Huafeng Zhang, Wei Jiang, Rongbin Zhou
The dysregulation of NLRP3 inflammasome can cause uncontrolled inflammation and drive the development of a wide variety of human diseases, but the medications targeting NLRP3 inflammasome are not available in clinic. Here, we show that tranilast (TR), an old anti-allergic clinical drug, is a direct NLRP3 inhibitor. TR inhibits NLRP3 inflammasome activation in macrophages, but has no effects on AIM2 or NLRC4 inflammasome activation. Mechanismly, TR directly binds to the NACHT domain of NLRP3 and suppresses the assembly of NLRP3 inflammasome by blocking NLRP3 oligomerization...
March 12, 2018: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29511112/we-aim2-inflame
#12
EDITORIAL
Andreas Linkermann, Simon P Parmentier, Christian Hugo
No abstract text is available yet for this article.
March 6, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29510138/aim2-accelerates-the-atherosclerotic-plaque-progressions-in-apoe-mice
#13
Jinyu Pan, Li Han, Jun Guo, Xuyang Wang, Dian Liu, Jingjing Tian, Mingjun Zhang, Fengshuang An
Plaque formation is initiated and triggered by cell death in the vascular wall, which gradually leads to the progression of atherosclerosis. Pyroptosis is a newly discovered form of programmed cell death. Absent in melanoma 2 (AIM2), a member of the HIN-200 protein family, plays an important role in activating inflammasomes. However, the role and mechanism of AIM2 in atherosclerotic plaque progression has not been thoroughly elucidated to date. The effect of pyroptosis and the mechanism for this effect were investigated in apolipoprotein E-deficient (ApoE-/-) mice...
March 3, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29508025/cd137l-dendritic-cells-induce-potent-response-against-cancer-associated-viruses-and-polarize-human-cd8-t-cells-to-tc1-phenotype
#14
Bhushan Dharmadhikari, Emily Nickles, Zulkarnain Harfuddin, Nur Diana Binte Ishak, Qun Zeng, Antonio Bertoletti, Herbert Schwarz
Therapeutic tumor vaccination based on dendritic cells (DC) is safe; however, its efficacy is low. Among the reasons for only a subset of patients benefitting from DC-based immunotherapy is an insufficient potency of in vitro generated classical DCs (cDCs), made by treating monocytes with GM-CSF + IL-4 + maturation factors. Recent studies demonstrated that CD137L (4-1BBL, TNFSF9) signaling differentiates human monocytes to a highly potent novel type of DC (CD137L-DCs) which have an inflammatory phenotype and are closely related to in vivo DCs...
March 5, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29478775/dampened-sting-dependent-interferon-activation-in-bats
#15
Jiazheng Xie, Yang Li, Xurui Shen, Geraldine Goh, Yan Zhu, Jie Cui, Lin-Fa Wang, Zheng-Li Shi, Peng Zhou
Compared with terrestrial mammals, bats have a longer lifespan and greater capacity to co-exist with a variety of viruses. In addition to cytosolic DNA generated by these viral infections, the metabolic demands of flight cause DNA damage and the release of self-DNA into the cytoplasm. However, whether bats have an altered DNA sensing/defense system to balance high cytosolic DNA levels remains an open question. We demonstrate that bats have a dampened interferon response due to the replacement of the highly conserved serine residue (S358) in STING, an essential adaptor protein in multiple DNA sensing pathways...
February 6, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/29448104/aim2-regulates-vascular-smooth-muscle-cell-migration-in-atherosclerosis
#16
Jinyu Pan, Lu Lu, Xuyang Wang, Dian Liu, Jingjing Tian, Hui Liu, Mingjun Zhang, Fengqin Xu, Fengshuang An
BACKGROUND: Atherosclerosis (AS) is a common pathological basis of various cardiovascular and cerebrovascular diseases. Plaque formation is initiated and triggered by vascular smooth musclecells (VSMCs) migration in vascular wall, which gradually aggravates atherosclerosis progression. Absent in melanoma 2 (AIM2), a member of HIN-200 family, plays an important role in activating inflammasome. However, the role of AIM2 in atherosclerotic plaque progression outside of the inflammasome has not yet been reported...
February 12, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29447697/herpes-simplex-virus-1-vp22-inhibits-aim2-dependent-inflammasome-activation-to-enable-efficient-viral-replication
#17
Yuhei Maruzuru, Takeshi Ichinohe, Ryota Sato, Kensuke Miyake, Tokuju Okano, Toshihiko Suzuki, Takumi Koshiba, Naoto Koyanagi, Shumpei Tsuda, Mizuki Watanabe, Jun Arii, Akihisa Kato, Yasushi Kawaguchi
The AIM2 inflammasome is activated by DNA, leading to caspase-1 activation and release of pro-inflammatory cytokines interleukin 1β (IL-1β) and IL-18, which are critical mediators in host innate immune responses against various pathogens. Some viruses employ strategies to counteract inflammasome-mediated induction of pro-inflammatory cytokines, but their in vivo relevance is less well understood. Here we show that the herpes simplex virus 1 (HSV-1) tegument protein VP22 inhibits AIM2-dependent inflammasome activation...
February 14, 2018: Cell Host & Microbe
https://www.readbyqxmd.com/read/29446207/vegf-mitigates-histone-induced-pyroptosis-in-the-remote-liver-injury-associated-with-renal-allograft-ischemia-reperfusion-injury-in-rats
#18
Hailin Zhao, Han Huang, Azeem Alam, Qian Chen, Ka Chuen Suen, Jiang Cui, Qizhe Sun, Rele Ologunde, Wenwen Zhang, Qingquan Lian, Daqing Ma
Clinical evidence indicated a possible link between renal injury and remote liver injury. Herein, we investigated whether extracellular histone mediates remote hepatic damage following renal graft ischemia-reperfusion injury, whilst vascular endothelial growth factor (VEGF) is protective against remote hepatic injury. In vitro, hepatocyte HepG2 cultures were treated with histone. In vivo, the Brown-Norway renal graft was stored in 4°C preserving solution for 24 hours and then transplanted into Lewis rat recipient; blood samples and livers from recipients were harvested 24 hours after surgery...
February 15, 2018: American Journal of Transplantation
https://www.readbyqxmd.com/read/29440442/digital-signaling-network-drives-the-assembly-of-the-aim2-asc-inflammasome
#19
Mariusz Matyszewski, Seamus R Morrone, Jungsan Sohn
The AIM2-ASC inflammasome is a filamentous signaling platform essential for mounting host defense against cytoplasmic dsDNA arising not only from invading pathogens but also from damaged organelles. Currently, the design principles of its underlying signaling network remain poorly understood at the molecular level. We show here that longer dsDNA is more effective in inducing AIM2 assembly, its self-propagation, and downstream ASC polymerization. This observation is related to the increased probability of forming the base of AIM2 filaments, and indicates that the assembly discerns small dsDNA as noise at each signaling step...
February 12, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29439156/macrophage-uptake-of-necrotic-cell-dna-activates-the-aim2-inflammasome-to-regulate-a-proinflammatory-phenotype-in-ckd
#20
Takanori Komada, Hyunjae Chung, Arthur Lau, Jaye M Platnich, Paul L Beck, Hallgrimur Benediktsson, Henry J Duff, Craig N Jenne, Daniel A Muruve
Nonmicrobial inflammation contributes to CKD progression and fibrosis. Absent in melanoma 2 (AIM2) is an inflammasome-forming receptor for double-stranded DNA. AIM2 is expressed in the kidney and activated mainly by macrophages. We investigated the potential pathogenic role of the AIM2 inflammasome in kidney disease. In kidneys from patients with diabetic or nondiabetic CKD, immunofluorescence showed AIM2 expression in glomeruli, tubules, and infiltrating leukocytes. In a mouse model of unilateral ureteral obstruction (UUO), Aim2 deficiency attenuated the renal injury, fibrosis, and inflammation observed in wild-type (WT) littermates...
February 9, 2018: Journal of the American Society of Nephrology: JASN
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