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https://www.readbyqxmd.com/read/28099758/melatonin-alleviates-cadmium-induced-liver-injury-by-inhibiting-the-txnip-nlrp3-inflammasome
#1
Zhengwang Cao, Yiliang Fang, Yonghui Lu, Dunxian Tan, Changhong Du, Yuming Li, Qinlong Ma, Junmei Yu, Mengyan Chen, Chao Zhou, Liping Pei, Lei Zhang, Haiying Ran, Mindi He, Zhengping Yu, Zhou Zhou
Cadmium (Cd) is a persistent environmental and occupational contaminant that accumulates in the liver and induces oxidative stress and inflammation. Melatonin possesses potent hepatoprotective properties against the development and progression of acute and chronic liver injury. Nevertheless, the molecular mechanism underlying the protective effects of melatonin against Cd-induced hepatotoxicity remains obscure. In the present study, we aimed to investigate the effects of melatonin on Cd-induced liver inflammation and hepatocyte death...
January 18, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28093447/inflammasomes-and-cancer
#2
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/28092085/evidence-that-nf-%C3%AE%C2%BAb-and-mapk-signaling-promotes-nlrp-inflammasome-activation-in-neurons-following-ischemic-stroke
#3
David Yang-Wei Fann, Yun-An Lim, Yi-Lin Cheng, Ker-Zhing Lok, Prasad Chunduri, Sang-Ha Baik, Grant R Drummond, S Thameem Dheen, Christopher G Sobey, Dong-Gyu Jo, Christopher Li-Hsian Chen, Thiruma V Arumugam
Multi-protein complexes, termed "inflammasomes," are known to contribute to neuronal cell death and brain injury following ischemic stroke. Ischemic stroke increases the expression and activation of nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) Pyrin domain containing 1 and 3 (NLRP1 and NLRP3) inflammasome proteins and both interleukin (IL)-1β and IL-18 in neurons. In this study, we provide evidence that activation of either the NF-κB and MAPK signaling pathways was partly responsible for inducing the expression and activation of NLRP1 and NLRP3 inflammasome proteins and that these effects can be attenuated using pharmacological inhibitors of these two pathways in neurons and brain tissue under in vitro and in vivo ischemic conditions, respectively...
January 14, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28077445/human-antiviral-protein-ifix-suppresses-viral-gene-expression-during-hsv-1-infection-and-is-counteracted-by-virus-induced-proteasomal-degradation
#4
Marni S Crow, Ileana M Cristea
The interferon inducible protein X (IFIX), a member of the PYHIN family, was recently recognized as an antiviral factor against infection with herpes simplex virus 1 (HSV-1). IFIX binds viral DNA upon infection and promotes antiviral cytokines expression. How IFIX exerts its host defense functions and whether it is inhibited by the virus remains unknown. Here, we integrated live cell microscopy, proteomics, IFIX domain characterization, and molecular virology to investigate IFIX regulation and antiviral functions during HSV-1 infection...
January 11, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28068647/berberine-an-isoquinoline-alkaloid-suppresses-txnip-mediated-nlrp3-inflammasome-activation-in-msu-crystal-stimulated-raw-264-7-macrophages-through-the-upregulation-of-nrf2-transcription-factor-and-alleviates-msu-crystal-induced-inflammation-in-rats
#5
Palani Dinesh, MahaboobKhan Rasool
The current study was designed to investigate the therapeutic potential of berberine on monosodium urate (MSU) crystal stimulated RAW 264.7 macrophages and in MSU crystal induced rats. Our results indicate that berberine (25, 50 and 75μM) suppressed the levels of pro-inflammatory cytokines (interleukin-1beta (IL-1β) and tumor necrosis factor alpha (TNFα)) and intracellular reactive oxygen species in MSU crystal stimulated RAW 264.7 macrophages. The mRNA expression levels of IL-1β, caspase 1, nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3), thioredoxin interacting protein (TXNIP) and kelch-like ECH-associated protein 1 (Keap1) were found downregulated with the upregulation of nuclear factor erythroid-2-related factor 2 (Nrf2) transcription factor and its associated anti-oxidant enzymes: Heme oxygenase I (HO-1), superoxide dismutase (SOD1), glutathione peroxidase (GPx), NADPH quinone oxidoreductase-1 (NQO1) and catalase (CAT) in MSU crystal stimulated RAW 264...
January 6, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28065854/the-mechanism-of-nlrp3-inflammasome-initiation-trimerization-but-not-dimerization-of-the-nlrp3-pyrin-domain-induces-robust-activation-of-il-1%C3%AE
#6
Petra Sušjan, Samo Roškar, Iva Hafner-Bratkovič
NLRP3 inflammasome is a multiprotein platform for the activation of caspase-1. Despite the increasing number of reports linking NLRP3 inflammasome to a variety of diseases, the mechanism behind the NLRP3 activation remains elusive, especially in terms of the early stages which are critical to the NLRP3 inflammasome assembly. In the present study we aimed to determine the minimal oligomerization state required for the NLRP3 inflammasome activation. For this purpose, NLRP3 pyrin domain (NLRP3(PYD)) was fused to various dimerization and trimerization domains...
January 5, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28064010/vascular-endothelial-cells-senescence-is-associated-with-nod-like-receptor-family-pyrin-domain-containing-3-nlrp3-inflammasome-activation-via-reactive-oxygen-species-ros-thioredoxin-interacting-protein-txnip-pathway
#7
Yanlin Yin, Zhihui Zhou, Weiwei Liu, Qun Chang, Guanqun Sun, Yalei Dai
Endothelial dysfunction caused by endothelial cells senescence and chronic inflammation is tightly linked to the development of cardiovascular diseases. NLRP3 (NOD-like receptor family pyrin domain-containing3) inflammasome plays a central role in inflammatory response that is associated with diverse inflammatory diseases. This study explores the effects and possible mechanisms of NLRP3 inflammasome in endothelial cells senescence. Results show an increment of pro-inflammatory cytokine interleukin (IL) -1β secretion and caspase-1 activation during the senescence of endothelial cells induced by bleomycin...
January 4, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28062222/absent-in-melanoma-2-proteins-in-sle
#8
REVIEW
Divaker Choubey, Ravichandran Panchanathan
Type I interferons (IFN-α/β)-inducible PYRIN and HIN domain-containing protein family includes Absent in Melanoma 2 (murine Aim2 and human AIM2), murine p202, and human PYRIN-only protein 3 (POP3). The generation of Aim2-deficient mice indicated that the Aim2 protein is essential for inflammasome activation, resulting in the secretion of interleukin-1β (IL-1β) and IL-18 and cell death by pyroptosis. Further, Aim2-deficiency also increased constitutive expression of the IFN-β and expression of the p202 protein...
January 3, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28056339/asbestos-induced-mesothelial-to-fibroblastic-transition-is-modulated-by-the-inflammasome
#9
Joyce K Thompson, Maximilian B MacPherson, Stacie L Beuschel, Arti Shukla
Despite the causal relationship established between malignant mesothelioma (MM) and asbestos exposure, the exact mechanism by which asbestos induces this neoplasm and other asbestos-related diseases is still not well understood. MM is characterized by chronic inflammation, which is believed to play an intrinsic role in the origin of this disease. We recently found that asbestos activates the nod-like receptor family member containing a pyrin domain 3 (NLRP3) inflammasome in a protracted manner, leading to an up-regulation of IL-1β and IL-18 production in human mesothelial cells...
January 2, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28052268/microbiota-plays-a-key-role-in-non-steroidal-anti-inflammatory-drug-induced-small-intestinal-damage
#10
Koji Otani, Tetsuya Tanigawa, Toshio Watanabe, Sunao Shimada, Yuji Nadatani, Yasuaki Nagami, Fumio Tanaka, Noriko Kamata, Hirokazu Yamagami, Masatsugu Shiba, Kazunari Tominaga, Yasuhiro Fujiwara, Tetsuo Arakawa
BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) damage the small intestine by causing multiple erosions and ulcers. However, to date, no established therapies and prophylactic agents are available to treat such damages. We reviewed the role of intestinal microbiota in NSAID-induced intestinal damage and identified potential therapeutic candidates. SUMMARY: The composition of the intestinal microbiota is an important factor in the pathophysiology of NSAID-induced small intestinal damage...
2017: Digestion
https://www.readbyqxmd.com/read/28051086/neutrophilic-nlrp3-inflammasome-dependent-il-1%C3%AE-secretion-regulates-the-%C3%AE-%C3%AE-t17-cell-response-in-respiratory-bacterial-infections
#11
M Hassane, D Demon, D Soulard, J Fontaine, L E Keller, E C Patin, R Porte, I Prinz, B Ryffel, A Kadioglu, J-W Veening, J-C Sirard, C Faveeuw, M Lamkanfi, F Trottein, C Paget
Traditionally regarded as simple foot soldiers of the innate immune response limited to the eradication of pathogens, neutrophils recently emerged as more complex cells endowed with a set of immunoregulatory functions. Using a model of invasive pneumococcal disease, we highlighted an unexpected key role for neutrophils as accessory cells in innate interleukin (IL)-17A production by lung resident Vγ6Vδ1(+) T cells via nucleotide-binding oligomerization domain receptor, pyrin-containing 3 (NLRP3) inflammasome-dependent IL-1β secretion...
January 4, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28040706/familial-mediterranean-fever-associated-diseases-in-children
#12
Z Birsin Özçakar, Nilgün Çakar, Nermin Uncu, Banu Acar Çelikel, Fatoş Yalçınkaya
BACKGROUND: MEditerranean FeVer (MEFV) gene encodes for the pyrin protein and a mutated pyrin is associated with a prolonged or augmented inflammation. Hence, various diseases were reported to be associated with familial Mediterranean fever (FMF) or carriers of MEFV mutations. However, systematic evaluation of all associated diseases in children with FMF has not been done previously. AIM: The aim of this study was to investigate the frequency and type of FMF-associated diseases in children...
December 30, 2016: QJM: Monthly Journal of the Association of Physicians
https://www.readbyqxmd.com/read/28019679/inflammasome-activation-and-innate-immunity-in-alzheimer-s-disease
#13
Michael T Heneka
Activation of innate immunity and the assembly of microglial cells at sites of Alzheimer disease pathology has long been regarded as bystander phenomenon, which does not actively contribute to disease pathogenesis and progression. Recent data emerging from genetics, clinical imaging and animal experimentation point to an intimate and mutual interaction of innate immune mechanisms and neurodegenerative processes. NOD-like receptor (NLR) family, pyrin domain containing 3 and 1 inflammasomes, present in myeloid cells and neurons, respectively, represent key components of the innate immune reaction observed in Alzheimer patient brains...
December 26, 2016: Brain Pathology
https://www.readbyqxmd.com/read/28018446/familial-mediterranean-fever-presenting-as-fever-of-unknown-origin-in-korea
#14
Jun Hee Lee, Jong Hyun Kim, Jung Ok Shim, Kwang Chul Lee, Joo Won Lee, Jung Hwa Lee, Jae Jin Chae
Familial Mediterranean fever (FMF) is the most common Mendelian autoinflammatory disease, characterized by uncontrolled activation of the innate immune system that manifests as recurrent brief fever and polyserositis (e.g., peritonitis, pleuritic, and arthritis). FMF is caused by autosomal recessive mutations of the Mediterranean fever gene, MEFV which encodes the pyrin protein. Although FMF predominantly affects people from Mediterranean and Middle Eastern ethnic origins, 3 cases of FMF have been reported in Korea since 2012...
November 2016: Korean Journal of Pediatrics
https://www.readbyqxmd.com/read/28013367/actin-polymerization-plays-a-significant-role-in-asbestos-induced-inflammasome-activation-in-mesothelial-cells-in-vitro
#15
Maximilian MacPherson, Catherine Westbom, Helen Kogan, Arti Shukla
Asbestos exposure leads to malignant mesothelioma (MM), a deadly neoplasm of mesothelial cells of various locations. Although there is no doubt about the role of asbestos in MM tumorigenesis, mechanisms are still not well explored. Recently, our group demonstrated that asbestos causes inflammasome priming and activation in mesothelial cells, which in part is dependent on oxidative stress. Our current study sheds light on yet another mechanism of inflammasome activation by asbestos. Here we show the role of actin polymerization in asbestos-induced activation of the nod-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome...
December 24, 2016: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/28012441/ugonin-u-stimulates-nlrp3-inflammasome-activation-and-enhances-inflammasome-mediated-pathogen-clearance
#16
Chun-Yu Chen, Chuan-Hui Yang, Yung-Fong Tsai, Chih-Chuang Liaw, Wen-Yi Chang, Tsong-Long Hwang
The NOD-like receptor pyrin domain 3 (NLRP3) inflammasome contains Nod-like receptors, a subclass of pattern recognition receptors, suggesting that this complex has a prominent role in host defenses. Various structurally diverse stimulators activate the NLRP3 inflammasome through different signaling pathways. We previously reported that ugonin U (UgU), a natural flavonoid isolated from Helminthostachys zeylanica (L) Hook, directly stimulates phospholipase C (PLC) and triggers superoxide release in human neutrophils...
December 18, 2016: Redox Biology
https://www.readbyqxmd.com/read/28011505/association-of-inflammasome-components-in-background-liver-with-poor-prognosis-after-curatively-resected-hepatocellular-carcinoma
#17
Fuminori Sonohara, Yoshikuni Inokawa, Mitsuro Kanda, Yoko Nishikawa, Suguru Yamada, Tsutomu Fujii, Hiroyuki Sugimoto, Yasuhiro Kodera, Shuji Nomoto
BACKGROUND/AIM: Inflammasomes are multiprotein complexes that evoke key inflammatory cascades. The present study evaluated the influence of inflammasome component expression in non-tumorous tissue on postsurgical hepatocellular carcinoma (HCC) prognosis. MATERIALS AND METHODS: The expressions of candidate genes were investigated using real-time quantitative reverse-transcription polymerase chain reaction in resected HCC cases. In order to identify potential prognostic factors, statistical analyses were performed for each gene...
January 2017: Anticancer Research
https://www.readbyqxmd.com/read/28005072/human-umbilical-cord-blood-stem-cells-direct-macrophage-polarization-and-block-inflammasome-activation-to-alleviate-rheumatoid-arthritis
#18
Tae-Hoon Shin, Hyung-Sik Kim, Tae-Wook Kang, Byung-Chul Lee, Hwa-Yong Lee, Yoon-Jin Kim, Ji-Hee Shin, Yoojin Seo, Soon Won Choi, Seunghee Lee, Kichul Shin, Kwang-Won Seo, Kyung-Sun Kang
Rheumatoid arthritis (RA) is a long-lasting intractable autoimmune disorder, which has become a substantial public health problem. Despite widespread use of biologic drugs, there have been uncertainties in efficacy and long-term safety. Mesenchymal stem cells (MSCs) have been suggested as a promising alternative for the treatment of RA because of their immunomodulatory properties. However, the precise mechanisms of MSCs on RA-related immune cells are not fully elucidated. The aim of this study was to investigate the therapeutic potential of human umbilical cord blood-derived MSCs (hUCB-MSCs) as a new therapeutic strategy for patients with RA and to explore the mechanisms underlying hUCB-MSC-mediated immunomodulation...
December 22, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/28004443/amyloid-%C3%AE-induces-nlrp3-inflammasome-activation-in-retinal-pigment-epithelial-cells-via-nadph-oxidase-and-mitochondria-dependent-ros-production
#19
Ke Wang, Yong Yao, Xue Zhu, Kai Zhang, Fanfan Zhou, Ling Zhu
Amyloid β (Aβ)-induced chronic inflammation is believed to be a key pathogenic process in early-stage age-related macular degeneration (AMD). Nucleotide oligomerization domain (NOD)-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation triggered by Aβ is responsible for retinal pigment epithelium (RPE) dysfunction in the onset of AMD; however, the detailed molecular mechanism remains unclear. In this study, we investigated the involvement of NADPH oxidase- and mitochondria-derived reactive oxygen species (ROS) in the process of Aβ1-40 -induced NLRP3 inflammasome activation in LPS-primed ARPE-19 cells...
December 22, 2016: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/28001092/familial-mediterranean-fever-with-p369s-r408q-exon3-variant-in-pyrin-presenting-as-symptoms-of-pfapa
#20
Keiko Yamagami, Tomoyuki Nakamura, Ryota Nakamura, Yusuke Hanioka, Kaori Seki, Hiroshi Chiba, Keiko Kobayashi, Kazunaga Agematsu
Familial Mediterranean fever (FMF) can be classified into typical and incomplete/atypical types. Periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis (PFAPA) syndrome-like symptoms has been found in atypical type carrying P369S-R408Q mutations in the responsible gene MEFV. A 28-year-old female with recurrent fever and her young sisters and mother, all of whom had tonsillectomy for tonsillitis, carried heterozygous alterations involving E148Q/P369S/R408Q. A diagnosis of atypical FMF, MEFV exon3 variants with PFAPA syndrome-like symptoms, was made...
December 21, 2016: Modern Rheumatology
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