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https://www.readbyqxmd.com/read/29150951/inflammasome-its-role-in-traumatic-brain-and-spinal-cord-injury
#1
REVIEW
Keywan Mortezaee, Neda Khanlarkhani, Cordian Beyer, Adib Zendedel
Traumatic brain injury (TBI) and spinal cord injury (SCI) are pathological events that lead to neuropathological conditions which have in consequence the initiation of pro-inflammatory cytokine production. Neuroinflammation plays a key role in the secondary phase of both TBI and SCI after initial cell death. Activation of cytoplasmic inflammasome complexes is regarded as the essential step of neuroinflammation and a key trigger for neuronal death called pyroptosis. Inflammasome complexes are involved in activation of caspase-1 which catalyzes the cleavage of pro-interleukins into their active forms (including interleukin-18 (IL-18) and IL-1β)...
November 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29150554/cancer-cells-induce-interleukin-22-production-from-memory-cd4-t-cells-via-interleukin-1-to-promote-tumor-growth
#2
Cornelia Voigt, Peter May, Adrian Gottschlich, Anamarija Markota, Daniel Wenk, Inga Gerlach, Sebastian Voigt, Georgios T Stathopoulos, Kristina A M Arendt, Constanze Heise, Felicitas Rataj, Klaus-Peter Janssen, Melanie Königshoff, Hauke Winter, Isabelle Himsl, Wolfgang E Thasler, Max Schnurr, Simon Rothenfußer, Stefan Endres, Sebastian Kobold
IL-22 has been identified as a cancer-promoting cytokine that is secreted by infiltrating immune cells in several cancer models. We hypothesized that IL-22 regulation would occur at the interface between cancer cells and immune cells. Breast and lung cancer cells of murine and human origin induced IL-22 production from memory CD4(+) T cells. In the present study, we found that IL-22 production in humans is dependent on activation of the NLRP3 inflammasome with the subsequent release of IL-1β from both myeloid and T cells...
November 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29150317/amp-activated-protein-kinase-regulation-of-the-nlrp3-inflammasome-during-aging
#3
REVIEW
Mario D Cordero, Matthew R Williams, Bernhard Ryffel
The NLRP3 inflammasome has recently emerged as an unexpected marker of stress and metabolic risk and has also been implicated in the development of major aging-related diseases such as gout, type 2 diabetes, obesity, cancer, and neurodegenerative and cardiovascular disorders. Several pathways regulating the NLRP3 inflammasome are currently being studied, but how the NLRP3 inflammasome is regulated remains unknown. AMP-activated protein kinase (AMPK), a central regulator of multiple metabolic pathways involved in the pathophysiology of aging and age-related diseases, has emerged as an important integrator of signals controlling inflammation including the inflammasome...
November 14, 2017: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/29149703/quercetin-attenuates-collagen-induced-arthritis-by-restoration-of-th17-treg-balance-and-activation-of-heme-oxygenase-1-mediated-anti-inflammatory-effect
#4
Yan Yang, Xu Zhang, Min Xu, Xin Wu, Feipeng Zhao, Chengzhi Zhao
Quercetin (QU) has been shown obvious anti-arthritic property in pre-clinical studies or clinical studies. Howbeit, the underlying mechanism of it is still not revealed distinctly and should be gotten further insight into. QU at a dosage of 150 mg/kg was administered orally in collagen-induced arthritis rats and then the clinical symptoms were monitored. The protein levels of Th17/Treg-related cytokines were determined by ELISA, and the mRNA levels of cytokines and transcription factors associated with the Th17 and Treg phenotypes were evaluated by real-time PCR, the proportions of Th17 and Treg cells were assessed by flow cytometry...
November 14, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/29148409/a-high-and-equal-prevalence-of-the-q703k-variant-in-nlrp3-patients-with-autoinflammatory-symptoms-and-ethnically-matched-controls
#5
Merav Lidar, Yael Brantz, Yael Shinar, Haike Reznik-Wolf, Avi Livneh, Ilan Ben Zvi, Rinat Cohen, Yaakov Berkun, Philip J Hashkes, Hagit Peleg, Aharon Kessel, Gleb Slobodin, Michael Rozenbaum, Ofra Goldzweig, Elon Pras
OBJECTIVES: Cryopyrin associated periodic syndromes (CAPS) comprise a spectrum of autoinflammatory disorders of varying severity caused by mutations in the NLRP3 gene. The NLRP3-Q703K allele has been reported both as a functional polymorphism and as a low penetrance mutation. METHODS: To describe the clinical phenotype of subjects with the Q703K allele and to report the frequency of this allele among patients with autoinflammatory symptoms and healthy controls. To this end, a cohort of 10 ethnically-matched controls per each Q703K-carrying patient, was composed...
October 6, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/29148034/role-of-p62-sqstm1-beyond-autophagy-a-lesson-learned-from-drug-induced-toxicity-in-vitro
#6
Fernando Alegre, Ángela B Moragrega, Miriam Polo, Alberto Marti-Rodrigo, Juan V Esplugues, Ana Blas-Garcia, Nadezda Apostolova
BACKGROUND AND PURPOSE: SQSTM1/p62 is a multifunctional, stress-induced, scaffold protein involved in multiple cellular processes including autophagic clearance, regulation of inflammatory responses and redox homeostasis. Alterations in its function have been associated with a long list of human pathologies such as neurodegenerative, metabolic and bone diseases (down-regulation), and cancerogenesis (up-regulation). However, its role in the off-target effects of clinically used drugs is still not understood...
November 17, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29147756/locus-and-gene-based-gwas-meta-analysis-identifies-new-diabetic-nephropathy-genes
#7
Mohammad Saeed
Objective Assimilation of SNPs Interacting in Synchrony (OASIS) is a locus-based clustering algorithm recently described that can potentially address false positives and negatives in genome-wide association studies (GWAS) of complex disorders. Diabetic nephropathy (DN) is incompletely understood due to a paucity of genes identified despite several GWAS. OASIS was applied to three DN dbGAP GWAS datasets (4725 subjects; 1.06 million SNPs). OASIS identified 19 DN genes which were verified using single variant replication in a standard association study and gene-based analysis using GATES...
November 16, 2017: Immunogenetics
https://www.readbyqxmd.com/read/29146733/effects-of-chronically-increased-vegf-a-on-the-aging-heart
#8
Alexander G Marneros
Whether approaches to chronically increase VEGF-A in the heart may have beneficial effects and prevent the development of heart failure, in part by improving cardiac perfusion, or whether this increase could have detrimental effects on cardiac performance in the aging heart, has not been tested yet. In this study, a genetic mouse model with a chronic increase in VEGF-A in the heart is shown to have increased cardiac angiogenesis and develop cardiac hypertrophy with enhanced basal cardiac performance with age progression...
November 16, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29146293/andrographolide-a-promising-therapeutic-agent-negatively-regulates-glial-cell-derived-neurodegeneration-of-prefrontal-cortex-hippocampus-and-working-memory-impairment
#9
Sudeshna Das, K P Mishra, Lilly Ganju, S B Singh
Over activation of glial cell derived innate immune factors induces neuro-inflammation that results in neurodegenerative disease, like working memory impairment. In this study, we have investigated the role of andrographolide, a major constituent of Andrographis paniculata plant, in reduction of reactive glial cell derived working memory impairment. Real time PCR, Western bloting, flow cytometric and immunofluorescence studies demonstrated that andrographolide inhibited lipopolysaccharide (LPS)-induced overexpression of HMGB1, TLR4, NFκB, COX-2, iNOS, and release of inflammatory mediators in primary mix glial culture, adult mice prefrontal cortex and hippocampus region...
November 8, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29145789/helicobacter-pylori-controls-nlrp3-expression-by-regulating-hsa-mir-223-3p-and-il-10-in-cultured-and-primary-human-immune-cells
#10
Suneesh Kumar Pachathundikandi, Steffen Backert
Inflammasome-mediated production of mature IL-1β and IL-18 cytokines represents an important innate immune response against infecting pathogens. Helicobacter pylori, one of the most successful and persistent human pathogens, induces severe inflammation leading to gastritis and more serious gastric diseases. H. pylori modulates different immune responses for its survival and inflammasome signaling is manipulated by the cag pathogenicity island ( cagPAI), urease and VacA cytotoxin. Here we report that H. pylori regulates NLRP3 expression, an inflammasome forming regulator, in infected THP-1 monocytes...
January 1, 2017: Innate Immunity
https://www.readbyqxmd.com/read/29145157/bmscs-derived-mir-223-containing-exosomes-contribute-to-liver-protection-in-experimental-autoimmune-hepatitis
#11
Lu Chen, Feng-Bin Lu, Da-Zhi Chen, Jin-Lu Wu, En-de Hu, Lan-Man Xu, Ming-Hua Zheng, Hui Li, Yu Huang, Xiao-Ya Jin, Yue-Wen Gong, Zhuo Lin, Xiao-Dong Wang, Yong-Ping Chen
Autoimmune hepatitis is a chronic inflammatory disease in the liver with potential to the development of liver fibrosis. Recent evidences suggest that bone marrow derived mesenchymal stem cells (BMSCs) may exert its therapeutic activity through exosomes. Moreover, miR-223 is highly expressed in BMSCs and plays an important role in autoimmune diseases. Therefore, in this study, hepatoprotective role of BMSCs and miR-223 was investigated in both mice and hepatocytes. Liver antigen S100 was used to establish autoimmune hepatitis model in mice while LPS and ATP were used to establish cell injury model in hepatocyte...
November 13, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29144508/ly6g-neutrophil-derived-mir-223-inhibits-the-nlrp3-inflammasome-in-mitochondrial-damp-induced-acute-lung-injury
#12
Zunyong Feng, Shimei Qi, Yue Zhang, Zhilin Qi, Liang Yan, Jing Zhou, Fang He, Qianqian Li, Yanyan Yang, Qun Chen, Shi Xiao, Qiang Li, Yang Chen, Yao Zhang
MicroRNA (miRNA) mediates RNA interference to regulate a variety of innate immune processes, but how miRNAs coordinate the mechanisms underlying acute lung injury/acute respiratory distress syndrome (ALI/ARDS) in patients with pulmonary inflammatory injury is still unknown. In this study, we demonstrated that miR-223 limits the number of Ly6G+ neutrophils and inhibits the activity of the NLRP3 inflammasome to alleviate ALI induced by mitochondrial damage-associated molecular patterns (DAMPs) (MTDs). miR-223 expression is increased in the lungs of MTD-induced mice or ARDS patients following trauma/transfusion or following the physiological remission of ALI/ARDS...
November 16, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29143812/the-nlrp3-inflammasome-in-acute-myocardial-infarction
#13
REVIEW
Stefano Toldo, Antonio Abbate
The heart is extremely sensitive to ischaemic injury. During an acute myocardial infarction (AMI) event, the injury is initially caused by reduced blood supply to the tissues, which is then further exacerbated by an intense and highly specific inflammatory response that occurs during reperfusion. Numerous studies have highlighted the central role of the NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome in this process. The inflammasome, an integral part of the innate immune system, is a macromolecular protein complex that finely regulates the activation of caspase 1 and the production and secretion of powerful pro-inflammatory cytokines such as IL-1β and IL-18...
November 16, 2017: Nature Reviews. Cardiology
https://www.readbyqxmd.com/read/29142418/marantodes-pumilum-blume-kuntze-inhibited-secretion-of-lipopolysaccharide-and-monosodium-urate-crystal-stimulated-cytokines-and-plasma-prostaglandin-e2
#14
Eldiza Puji Rahmi, Jamia Azdina Jamal, Endang Kumolosasi, Juriyati Jalil, Nor-Ashila Aladdin
Background: Marantodes pumilum is traditionally used for dysentery, gonorrhea, and sickness in the bones. Previous studies revealed its antibacterial and xanthine oxidase inhibitory activities. Objective: To evaluate the inhibitory effects of three M. pumilum varieties on the secretion of lipopolysaccharide (LPS)- and monosodium urate crystal (MSU)-induced cytokines and plasma prostaglandin E2 (PGE2) in vitro. Materials and Methods: The leaves and roots of M...
October 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/29141025/suppression-of-inflammatory-and-infection-responses-in-lung-macrophages-by-eucalyptus-oil-and-its-constituent-1-8-cineole-role-of-pattern-recognition-receptors-trem-1-and-nlrp3-the-map-kinase-regulator-mkp-1-and-nf%C3%AE%C2%BAb
#15
Niket Yadav, Harish Chandra
Eucalyptus oil (EO) used in traditional medicine continues to prove useful for aroma therapy in respiratory ailments; however, there is a paucity of information on its mechanism of action and active components. In this direction, we investigated EO and its dominant constituent 1,8-cineole (eucalyptol) using the murine lung alveolar macrophage (AM) cell line MH-S. In an LPS-induced AM inflammation model, pre-treatment with EO significantly reduced (P ≤0.01or 0.05) the pro-inflammatory mediators TNF-α, IL-1 (α and β), and NO, albeit at a variable rate and extent; 1,8-cineole diminished IL-1 and IL-6...
2017: PloS One
https://www.readbyqxmd.com/read/29140564/%C3%AE-catenin-and-il-1%C3%AE-dependent-cxcl10-production-drives-progression-of-disease-in-a-mouse-model-of-congenital-hepatic-fibrosis
#16
Eleanna Kaffe, Romina Fiorotto, Francesca Pellegrino, Valeria Mariotti, Mariangela Amenduni, Massimiliano Cadamuro, Luca Fabris, Mario Strazzabosco, Carlo Spirli
Congenital Hepatic Fibrosis (CHF), a genetic disease caused by mutations in the PKHD1 gene, encoding for the protein fibrocystin (FPC), is characterized by biliary dysgenesis, progressive portal fibrosis, and by a PKA-mediated activating phosphorylation of β-Catenin at Ser675. Biliary structures of Pkhd1(del4/del4) mice, a mouse model of CHF, secrete CXCL10 a chemokine able to recruit macrophages. The aim of this study is to clarify whether CXCL10 plays a pathogenetic role in disease progression in CHF/CD and to understand the mechanisms leading to increased CXCL10 secretion...
November 15, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29138474/phagocytosis-of-environmental-or-metabolic-crystalline-particles-induces-cytotoxicity-by-triggering-necroptosis-across-a-broad-range-of-particle-size-and-shape
#17
Mohsen Honarpisheh, Orestes Foresto-Neto, Jyaysi Desai, Stefanie Steiger, Lidia Anguiano Gómez, Bastian Popper, Peter Boor, Hans-Joachim Anders, Shrikant R Mulay
In crystallopathies, crystals or crystalline particles of environmental and metabolic origin deposit within tissues, induce inflammation, injury and cell death and eventually lead to organ-failure. The NLRP3-inflammasome is involved in mediating crystalline particles-induced inflammation, but pathways leading to cell death are still unknown. Here, we have used broad range of intrinsic and extrinsic crystal- or crystalline particle-sizes and shapes, e.g. calcium phosphate, silica, titanium dioxide, cholesterol, calcium oxalate, and monosodium urate...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29137224/role-of-the-inflammasome-in-chronic-obstructive-pulmonary-disease-copd
#18
Chiara Colarusso, Michela Terlizzi, Antonio Molino, Aldo Pinto, Rosalinda Sorrentino
Inflammation is central to the development of chronic obstructive pulmonary disease (COPD), a pulmonary disorder characterized by chronic bronchitis, chronic airway obstruction, emphysema, associated to progressive and irreversible decline of lung function. Emerging genetic and pharmacological evidence suggests that IL-1-like cytokines are highly detected in the sputum and broncho-alveolar lavage (BAL) of COPD patients, implying the involvement of the multiprotein complex inflammasome. So far, scientific evidence has focused on nucleotide-binding oligomerization domain-like receptors protein 3 (NLRP3) inflammasome, a specialized inflammatory signaling platform that governs the maturation and secretion of IL-1-like cytokines through the regulation of caspase-1-dependent proteolytic processing...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29132140/mitochondria-targeted-peptide-attenuates-mitochondrial-dysfunction-controls-inflammation-and-protects-against-spinal-cord-injury-induced-lung-injury
#19
Liu-Long Zhu, Mao-Qiang Li, Fan He, Shao-Bo Zhou, Wu Jiang
BACKGROUND/AIMS: Spinal cord injury (SCI) is a common and devastating disease, which results in systemic inflammatory response syndrome and secondary lung injury. Mitochondrial dysfunction and inflammation are closely related to lung injury in diverse disease models. No studies have demonstrated the effects of mitochondrial targeted peptide SS-31 in a mouse model of SCI-induced lung injury. METHODS: Immediately after injury, mice in the treatment groups received a daily, single-dose intraperitoneal injection of SS-31 and for the next 2 days...
November 13, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29131546/polymeric-nanoparticles-induce-nlrp3-inflammasome-activation-and-promote-breast-cancer-metastasis
#20
Qinglian Hu, Fenghui Zhao, Fengliang Guo, Chengcheng Wang, Zhengwei Fu
Polymeric nanoparticles gain enormous interests in cancer therapy. Polyethylenimine (PEI) 25 kD is well known for its high transfection efficiency and cytotoxicity. PEI-CyD (PC) was previously synthesized by conjugating low molecular PEI (M w 600) with β-cyclodextrin (β-CyD), which is shown to induce lower cytotoxicity than PEI 25 kD. In the current study, the in vivo immune response of branched PEI 25 kD and PC is investigated. Compared to PC/pDNA, exposure of PEI 25kD/pDNA induces higher level of immune-stimulation evidenced by the increased spleen weight, phagocytic capacity of peritoneal macrophage, and proinflammatory cytokines in serum and liver...
November 13, 2017: Macromolecular Bioscience
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