المؤلفون: Igor Piotrowski, Wiktoria Maria Suchorska, Katarzyna Kulcenty

المصدر: Reports of Practical Oncology and Radiotherapy

مصطلحات موضوعية: Angiogenesis, STAT3, signal transducer and activator of transcription 3, NFκB, nuclear factor kappa-light-chain-enhancer of activated B cells, Original research article, PTHrP, parathyroid hormone related protein, MPO, myeloperoxidase, CDH1, cadherin 1, 030218 nuclear medicine & medical imaging, TNF-α, tumour necrosis factor α, 0302 clinical medicine, GI, gastrointensinal cancer, TNFR2, Tumor necrosis factor receptor 2, Cancer, TGF-β, transforming growth factor β, ROS, reactive oxigen species, EP, receptor - prostaglandin receptor, NSAIDs, non-steroidal anti-inflammatory drugs, Extravasation, IL-6, interleukin 6, Oncology, NADPH, nicotynamide adenine dinucleotide phosphate hydrogen, 030220 oncology & carcinogenesis, iNOS, inducible nitric oxide synthase, medicine.symptom, ANGPTL4, angiopoietin-like 4, Inflammation, NK, natural killer cells, RNS, reactive nitrogen species, 03 medical and health sciences, Immune system, medicine, PGE2, prostaglandin E2, Radiology, Nuclear Medicine and imaging, Neoplastic transformation, TGFBRII, transforming growth factor, beta receptor II, EMT, epithelail to mesenchymal transition, NO, nitric oxide, Innate immune system, business.industry, medicine.disease, Tumor reccurence, TNFR1, Tumor necrosis factor receptor 1, bFGF, fibroblast growth factor, COX, cyclooxygenase, Cancer research, business, Wound healing, VEGF, vascular endothelail growth factor

الوصف: Tumor-promoting inflammation is one of the hallmarks of cancer. It has been shown that cancer development is strongly influenced by both chronic and acute inflammation process. Progress in research on inflammation revealed a connection between inflammatory processes and neoplastic transformation, the progression of tumour, and the development of metastases and recurrences. Moreover, the tumour invasive procedures (both surgery and biopsy) affect the remaining tumour cells by increasing their survival, proliferation and migration. One of the concepts explaining this phenomena is an induction of a wound healing response. While in normal tissue it is necessary for tissue repair, in tumour tissue, induction of adaptive and innate immune response related to wound healing, stimulates tumour cell survival, angiogenesis and extravasation of circulating tumour cells. It has become evident that certain types of immune response and immune cells can promote tumour progression more than others. In this review, we focus on current knowledge on carcinogenesis and promotion of cancer growth induced by inflammatory processes.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bf716b2f37949b02e2980273a453ab9eTest
http://europepmc.org/articles/PMC7191124Test

المؤلفون: Anna Shtro, Marina Dukhinova, Polina Kuchur, Elena Kokinos, Alexey Komissarov

المصدر: Cytokine & Growth Factor Reviews

مصطلحات موضوعية: TGFβ, Transforming growth factor beta, MIF, Macrophage migration inhibitory factor, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Cellular Immunology, Monocytes, CCL, CC–chemokine ligand, MCP, Monocyte chemoattractant protein, Immunology and Allergy, Medicine, Macrophage, MRC, Mannose receptor C-type, IL, Interleukin, SNP, Single nucleotide polymorphisms, PAMP, Pathogen-associated molecular pattern, NFκB, Nuclear factor kappa-light-chain-enhancer of activated B cells, GWAS, Genome-wide association studies GWAS, IFN, Interferon, Cytokine, medicine.anatomical_structure, Cytokines, COPD, Chronic obstructive lung disorder, medicine.symptom, CD, Cluster of differentiation, TF, Transcription factor, TLR, Toll-like receptor, Immunology, Context (language use), Inflammation, TNFα, Tumor necrosis factor alpha, General Biochemistry, Genetics and Molecular Biology, Article, PPAR, Peroxisome proliferator-activated receptor, CCR, Cc chemokine receptor, EGFR, Epidermal growth factor receptor, PTX, Pentraxin-related protein, Humans, MՓ, Macrophage, RNA, Ribonucleic acid, ComputingMethodologies_COMPUTERGRAPHICS, MHC, Major histocompatibility complex, business.industry, SARS-CoV-2, STAT, Signal transducer and activator of transcription, Monocyte, Macrophages, COVID-19, Pneumonia, Single nucleotide polymorphisms, medicine.disease, LPS, Lipopolysaccharides, CXCL, Chemokine (C-X-C motif) ligand, GMCSF, Granulocyte-macrophage colony-stimulating factor, business, Cytokine storm, IRF, Interferon regulatory factor

الوصف: Graphical abstract
Macrophages represent the first line of anti-pathogen defense - they encounter invading pathogens to perform the phagocytic activity, to deliver the plethora of pro- and anti-inflammatory cytokines, and to shape the tissue microenvironment. Throughout pneumonia course, alveolar macrophages and infiltrated blood monocytes produce increasing cytokine amounts, which activates the antiviral/antibacterial immunity but can also provoke the risk of the so-called cytokine “storm” and normal tissue damage. Subsequently, the question of how the cytokine spectrum is shaped and balanced in the pneumonia context remains a hot topic in medical immunology, particularly in the COVID19 pandemic era. The diversity in cytokine profiles, involved in pneumonia pathogenesis, is determined by the variations in cytokine-receptor interactions, which may lead to severe cytokine storm and functional decline of particular tissues and organs, for example, cardiovascular and respiratory systems. Cytokines and their receptors form unique profiles in individual patients, depending on the (a) microenvironmental context (comorbidities and associated treatment), (b) lung monocyte heterogeneity, and (c) genetic variations. These multidisciplinary strategies can be proactively considered beforehand and during the pneumonia course and potentially allow the new age of personalized immunotherapy.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b3a702ed645dea7807089e0c4d5edaaeTest
https://pubmed.ncbi.nlm.nih.gov/33342718Test

المؤلفون: Martina Poturnajova, Zuzana Kozovska, Miroslava Matuskova

المصدر: Cellular Signalling

مصطلحات موضوعية: SMAD4, Mothers against decapentaplegic homolog 4, TLX-1, T-cell leukemia homeobox protein 1, Bcl-2, B-cell lymphoma 2, apoptosis regulator, PPARβ/δ, Peroxisome-proliferator-activated receptor β/δ, Retinoic acid, Aldehyde dehydrogenase, NSPc1, Polycomb 1 of the nervous system, Transcriptional control, TGF- β, Transforming growth factor beta, DHT, Dihydrotestosterone, BRD4, bromodomain-containing protein 4, chemistry.chemical_compound, SRC, proto-oncogene tyrosine-protein kinase, MDR, multidrug resistance, RARRES1, Retinoic acid receptor responder 1, Neoplasms, EZH2, Enhancer of zeste homolog 2, HPCs, hematopoietic progenitors, MEK, Mitogen-activated protein kinase, Transcriptional regulation, Protein Isoforms, RAR, Retinoic acid receptor, cMET (HGFR), Hepatocyte growth factor receptor, TNBC, triple negative breast cancer, biology, Chemistry, HOX, Homeobox protein, ERK, Extracellular signal-regulated kinase, NFκB, Nuclear factor kappa-light-chain-enhancer of activated B cells, Stem cells marker, NANOG, homeobox protein, transcriptional factor, C/EBPβ, CCAAT/enhancer-binding protein β, HNSCC, Head and neck squamous Cancer, Aldehyde Oxidoreductases, Graphical Review, PCAF, acetyltransferase P300/CBP-associated factor, ER, Estrogen receptor, Cell biology, MMP, matrix metalloproteinase, Crosstalk (biology), Molecular regulation, S1P, Sphingosine-1-phosphate, IL-6, Interleukin 6, NRF2, Nuclear respiratory factor 1, SOX2, SRY (sex determining region Y)-box 2, Stem cell, EMT, epithelial-mesenchymal transition, SIRT2, Sirtuin 2, CD24, signal transducer 24, sialoglycoprotein, Gene isoform, atRA, all trans retinoic acid, GADD153, Growth arrest and DNA damage 153, SNAI2, (Slug) zinc finger protein 2, MUC1-C, Mucin 1 glycoprotein, subunit C, Tretinoin, CDK2, Cyclin- dependent kinase 2, CHOP, C/EBP homologous protein, PI3K, Phosphatidylinositol 3-kinase, Aldehyde Dehydrogenase 1 Family, CD44, homing cell adhesion molecule, BAX, Bcl-2-like protein 4, apoptosis regulator, TCF4 (TCF7L2), Transcription factor 7-like 2, HSP27, heat shock protein 27, ROS, reactive oxygen species, RA, Retinoic acid, Humans, BET, bromodomain and extraterminal protein family, RARE, RA responsive element, SNAI1, (Snail) zinc finger protein 1, DANCR (KIAA0114), Differentiation antagonizing non-protein coding RNA, PTEN, Phosphatase and tensin homolog, ALDH1A13, aldehyde dehydrogenase 1 isoforms A1, A3, Mechanism (biology), Retinal Dehydrogenase, mTOR, Mammalian target of rapamycin, RXR, Retinoid X receptor, Cell Biology, HGF, Hepatocyte growth factor, CSC, cancer stem cell, NQO1, NAD(P)H dehydrogenase [quinone] 1, STAT3, Signal transducer and activator of transcription 3, ALDH1A1, CD31, Platelet endothelial cell adhesion molecule 1, RD16, retinol dehydrogenase 16, DDIT3, DNA damage inducible transcript 3, NRAD1 (LINC00284), Non-coding RNA in the aldehyde dehydrogenase 1A pathway, biology.protein, AR, androgen receptor

الوصف: In some types of human cancer, aldehyde dehydrogenases represent stemness markers and their expression is associated with advanced disease stages and poor prognosis. Although several biological functions are mediated by their product Retinoid acid, the molecular mechanism is tissue-dependent and only partially understood. In this review, we summarize the current knowledge about the role of ALDH in solid tumours, especially ALDH1A1 and ALDH1A3 isoforms, regarding the molecular mechanism of their transcription and regulation, and their crosstalk with main molecular pathways resulting in the excessive proliferation, chemoresistance, stem cells properties and invasiveness. The recent knowledge of the regulatory effect of lnRNA on ALDH1A1 and ALDH1A3 is discussed too.
Highlights • Aldehyde dehydrogenases are important stem cell markers in many human cancer types. • ALDH1A1 or ALDH1A3 activation participates in tumour progression, chemoresistance, stem-cell properties and invasiveness. • ALDH1A1 interacts with oncogenic pathways Notch, NRF, CXCR4, Polycomb, MDR, and HOX.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1457905c555ffd74710c72192f7cc6ceTest
https://doi.org/10.1016/j.cellsig.2021.110120Test

المؤلفون: Hegedűs, Csaba, Kovács, Katalin, Polgár, Zsuzsanna, Regdon, Zsolt, Szabó, Éva, Robaszkiewicz, Agnieszka, Forman, Henry Jay, Martner, Anna, Virág, László

المصدر: Redox Biology, Vol 16, Iss, Pp 59-74 (2018)
Redox Biology

مصطلحات موضوعية: PARP1, Poly (ADP-ribose) polymerase 1, TGFβ, Transforming growth factor beta, GFR, growth factor receptor, NQO1, NAD(P)H:quinone oxidoreductase 1, DAMP, damage-associated molecular pattern, MAP, mitogen-activated protein, MAPKKK, mitogen-activated protein kinase kinase kinase, NAC, N-acetylcysteine, Free radicals, Review Article, PD-L1, Programmed death-ligand 1, Nrf2, nuclear factor erythroid 2-related factor 2, Antioxidants, Her/hER, human Estrogen Receptor, HDC, histamine dihydrochloride, ADCC, antibody-dependent cell-mediated cytotoxicity, ERK, extracellular signal-regulated kinase, HIF-1 α, hypoxia inducible factor 1α, IL-2, Interleukin-2, DCFH 2', 7'-dichlorodihydrofluorescein, GSH, glutathione, Elméleti orvostudományok, NOS, nitric oxide synthase, AML, acute myeloid leukemia, LPS, Lipopolysaccharide, lcsh:QH301-705.5, Cancer, FAS, first apoptosis signal, PBMC, Peripheral blood mononuclear cell, MΦ, macrophage, EGF, Epidermal growth factor, lcsh:Medicine (General), ImC, immaturemyeloid cell, PhGPx, phospholipid hydroperoxide glutathione peroxidase, PDGF, Platelet-derived growth factor, Chemotherapeutics, Antineoplastic Agents, PI3K, Phosphatidylinositol 3-kinase, DDR, DNA damage response, TAMs, tumor-associated macrophages, Humans, ILT, immunoglobulin like transcripts, KIR, killer immunoglobulin-like receptor, DDB, Biphenyl Dimethyl Dicarboxylate, CAF, cancer-associated fibroblast, CLs, cytotoxic lymphocytes, NO, nitric oxide, APE1, apurinic/apyrimidinic endonuclease 1, TRAIL, TNF-related apoptosis-inducing ligand, TrxR1, thioredoxin reductase 1, CTL, cytotoxic T lymphocyte, PD1, Programmed cell death protein 1, ASK-1, apoptosis signal-regulated kinase 1, HMGB1, high mobility group box 1, Redox regulation, PK, pyruvate kinase, Reactive Oxygen Species, ADCP, antibody-dependent cancer cell phagocytosis, eNOS, Endothelial NOS, cPLA, cytosolic phospholipase A, GST, Glutathione transferase, NSCLC, Non-Small Cell Lung Cancer, LOOH, lipid hydroperoxide, NFκB, nuclear factor kappa-light-chain-enhancer of activated B cells, VEGF, Vascular endothelial growth factor, ABC transporters, ATP-binding cassette transporters, PEDF, pigment epithelium derived factor, PGE2, Prostaglandin E2, MHC-I, major histocompatibility complex type I, M-CSF, macrophage colony-stimulating factor, Neoplasms, PDT, Photodynamic therapy, NK, Natural Killer cells, TNF, tumor necrosis factor, lcsh:R5-920, GPx, glutathione peroxidase, TCR, T cell receptor, Orvostudományok, MnTBAP, Mn(III)tetrakis (4-benzoic acid) porphyrin, Natural killer cells, DCs, dendritic cells, Oxidation-Reduction, Signal Transduction, MDSC, myeloid derived suppressor cell, TLR, Toll-like receptor, CTLA-4, cytotoxic T-lymphocyte-associated protein 4, EMT, epithelial mesenchymal transition, ER, Endoplasmic reticulum, Cytotoxic lymphocytes, Dox, doxorubicin, CAR-T cells, Chimeric Antigen Receptor T-Cell, SOD, superoxide dismutase, EGFR, Epidermal growth factor receptor, MDR, multiple drug resistance, DUOX, nicotinamide adenine dinucleotide phosphate (NADPH) dual oxidase, nNOS, Neuronal NOS, LPO, lipid peroxidation products, NADPH, nicotinamide adenine dinucleotide phosphate, NCR, natural cytotoxicity receptor, CLL, chronic lymphoid leukemia, Oxidative Stress, NOX, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, lcsh:Biology (General), GM-CSF, Granulocyte-macrophage colony-stimulating factor, ETO, etoposide, ONOO-, peroxynitrite

الوصف: Redox regulation has been proposed to control various aspects of carcinogenesis, cancer cell growth, metabolism, migration, invasion, metastasis and cancer vascularization. As cancer has many faces, the role of redox control in different cancers and in the numerous cancer-related processes often point in different directions. In this review, we focus on the redox control mechanisms of tumor cell destruction. The review covers the tumor-intrinsic role of oxidants derived from the reduction of oxygen and nitrogen in the control of tumor cell proliferation as well as the roles of oxidants and antioxidant systems in cancer cell death caused by traditional anticancer weapons (chemotherapeutic agents, radiotherapy, photodynamic therapy). Emphasis is also put on the role of oxidants and redox status in the outcome following interactions between cancer cells, cytotoxic lymphocytes and tumor infiltrating macrophages. Keywords: Cancer, Redox regulation, Natural killer cells, Cytotoxic lymphocytes, Chemotherapeutics, Free radicals, Antioxidants

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::153be7bc8a9501b142b779dbaf4a96d6Test
http://www.sciencedirect.com/science/article/pii/S2213231717309424Test

المؤلفون: Christoph Becker, Markus F. Neurath, Britta Siegmund, Eva Martini, Susanne M. Krug

المصدر: Cellular and Molecular Gastroenterology and Hepatology

مصطلحات موضوعية: 0301 basic medicine, Lgr5, leucine rich repeat containing G-protein coupled receptor 5, MLCK, myosin light chain kinase, NOD-2, nucleotide-binding oligomerization domain-containing protein 2, TAMP, tight junction–associated MARVEL protein, NFκB, nuclear factor kappa-light-chain-enhancer of activated B cells, Review, Biology, medicine.disease_cause, Inflammatory bowel disease, 03 medical and health sciences, Immune system, Fz, frizzled, Intestinal Epithelial Barrier, medicine, HD, humans α-defensin, TSLP, thymic stromal lymphopoietin, Barrier function, MARVEL, myelin and lymphocyte and related proteins for vesicle trafficking and membrane link, TNF, tumor necrosis factor, Crohn's disease, Lamina propria, IBD, inflammatory bowel disease, Hepatology, Gastroenterology, Immune-Epithelial Crosstalk, Immune dysregulation, IECs, intestinal epithelial cells, medicine.disease, Intestinal epithelium, Epithelium, IL, interleukin, STAT, signal transducer and activator of transcription, UC, ulcerative colitis, TJ, tight junction, 030104 developmental biology, medicine.anatomical_structure, Immunology, BMP, bone morphogenic protein, CD, Crohn's disease, JAMs, junctional adhesion molecules, Intestinal Inflammation

الوصف: The intestinal epithelium can be easily disrupted during gut inflammation as seen in inflammatory bowel disease (IBD), such as ulcerative colitis or Crohn's disease. For a long time, research into the pathophysiology of IBD has been focused on immune cell-mediated mechanisms. Recent evidence, however, suggests that the intestinal epithelium might play a major role in the development and perpetuation of IBD. It is now clear that IBD can be triggered by disturbances in epithelial barrier integrity via dysfunctions in intestinal epithelial cell-intrinsic molecular circuits that control the homeostasis, renewal, and repair of intestinal epithelial cells. The intestinal epithelium in the healthy individual represents a semi-permeable physical barrier shielding the interior of the body from invasions of pathogens on the one hand and allowing selective passage of nutrients on the other hand. However, the intestinal epithelium must be considered much more than a simple physical barrier. Instead, the epithelium is a highly dynamic tissue that responds to a plenitude of signals including the intestinal microbiota and signals from the immune system. This epithelial response to these signals regulates barrier function, the composition of the microbiota, and mucosal immune homeostasis within the lamina propria. The epithelium can thus be regarded as a translator between the microbiota and the immune system and aberrant signal transduction between the epithelium and adjacent immune cells might promote immune dysregulation in IBD. This review summarizes the important cellular and molecular barrier components of the intestinal epithelium and emphasizes the mechanisms leading to barrier dysfunction during intestinal inflammation.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::652386fd0b393e1492840efce66b33eeTest
https://doi.org/10.1016/j.jcmgh.2017.03.007Test

المؤلفون: Wendy B. Bollag, Joyce Gonzales

المصدر: Medical Hypotheses

مصطلحات موضوعية: 0301 basic medicine, Neonatal respiratory distress syndrome, Swine, NFκB, nuclear factor kappa-light-chain-enhancer of activated B cells, Pharmacology, PG, phosphatidylglycerol, chemistry.chemical_compound, 0302 clinical medicine, Pulmonary surfactant, Surfactant, Lung, Innate immunity, Phosphatidylglycerol, Type-II Pneumocytes, Phosphatidylglycerols, General Medicine, Pulmonary edema, medicine.anatomical_structure, sPLA2, secretory phospholipase A2, medicine.symptom, PAMP, pathogen-associated molecular pattern, Adult, Critical Illness, Pulmonary Edema, Inflammation, Article, 03 medical and health sciences, DAMP, danger- or damage-associated molecular pattern, medicine, Animals, Humans, TLR, toll-like receptor, ARDS, acute respiratory distress syndrome, Innate immune system, TNFα, tumor necrosis factor-alpha, SARS-CoV-2, business.industry, COVID-19, Pulmonary Surfactants, Models, Theoretical, medicine.disease, Immunity, Innate, IL, interleukin, COVID-19 Drug Treatment, 030104 developmental biology, chemistry, Alveolar Epithelial Cells, Cattle, business, 030217 neurology & neurosurgery

الوصف: A hypothesis concerning the potential utility of surfactant supplementation for the treatment of critically ill patients with COVID-19 is proposed, along with a brief summary of the data in the literature supporting this idea. It is thought that surfactant, which is already approved by the Food and Drug Administration for intratracheal administration to treat neonatal respiratory distress syndrome in pre-term infants, could benefit COVID-19-infected individuals by: (1) restoring surfactant damaged by lung infection and/or decreased due to the virus-induced death of the type II pneumocytes that produce it and (2) reducing surface tension to decrease the work of breathing and limit pulmonary edema. In addition, a constituent of surfactant, phosphatidylglycerol, could mitigate COVID-19-induced lung pathology by: (3) decreasing excessive innate immune system stimulation via its inhibition of toll-like receptor-2 and -4 activation by microbial components and cellular proteins released by damaged cells, thereby limiting inflammation and the resultant pulmonary edema, and (4) possibly blocking spread of the viral infection to non-infected cells in the lung. Therefore, it is suggested that surfactant preparations containing phosphatidylglycerol be tested for their ability to improve lung function in critically ill patients with COVID-19.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9aab1d0f9591c311581eee3e2369ebbbTest
https://doi.org/10.1016/j.mehy.2020.110277Test

المؤلفون: Daichi Aoki, Kyoichi Iizumi, Osamu Hosomi, Kaoru Uchida, Makoto Ogata, Shuri Akiyama, Susumu Tanaka, Yuzuru Kubohara, Kazuki Fujita

المصدر: Biochemistry and Biophysics Reports
Biochemistry and Biophysics Reports, Vol 19, Iss, Pp-(2019)

مصطلحات موضوعية: PMA, phorbol 12-myristate 13-acetate, 0301 basic medicine, Interleukin 2, CIIP, ConA-induced IL-2 production, NFκB, nuclear factor kappa-light-chain-enhancer of activated B cells, Biophysics, ConA, concanavalin A, PIIP, PMA/IM-induced IL-2 production, AP-1, activator protein 1, Biochemistry, Jurkat cells, lcsh:Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Immune system, IL-2, interleukin-2, medicine, lcsh:QD415-436, Viability assay, lcsh:QH301-705.5, Transcription factor, IM, ionomycin, Glucosamine, GlcNH2, glucosamine, biology, Immunosuppressive drug, Chemistry, NFAT, Melibiosamine, Cell biology, NFAT, nuclear factor of activated T-cells, 030104 developmental biology, lcsh:Biology (General), Concanavalin A, Cell culture, 030220 oncology & carcinogenesis, biology.protein, Jurkat cell, CsA, cyclosporine A, Research Article, MelNH2, melibiosamine, medicine.drug

الوصف: d-Glucosamine (GlcNH2) and several of its derivatives are known to possess immunosuppressive activities in various immune cell lines. The novel GlcNH2-containing oligosaccharide Galα1-6GlcNH2 (designated melibiosamine; MelNH2) is expected to be immunosuppressive also. In Jurkat cells (immortalized human T lymphocytes), interleukin 2 (IL-2) production (an index of the T-cell immune response) can be induced by stimulation with a mitogen, such as concanavalin A. Here, we compared the effects of GlcNH2 and MelNH2 on concanavalin A-induced IL-2 production (CIIP) in Jurkat cells and found that GlcNH2 and MelNH2 at millimolar levels both significantly suppressed CIIP without affecting cell viability. When we examined the effects of GlcNH2 and MelNH2 on the activation of the three transcription factors required for CIIP—NFAT (nuclear factor of activated T-cells), NFκB (nuclear factor kappa-light-chain-enhancer of activated B cells), and AP-1 (activator protein 1)—we found that GlcNH2 and MelNH2 both suppressed CIIP by inhibiting the activation of NFAT and NFκB, but, unlike GlcNH2, MelNH2 also promoted the activation of AP-1. These results suggest that MelNH2 may be a potentially useful lead compound for development as an immunosuppressive or anti-inflammatory drug.
Highlights • Immunosuppressive effects of MelNH2 (Galα1-6GlcNH2) were examined in Jurkat cells. • Concanavalin A induces IL-2 production in Jurkat cells. • MelNH2 at millimolar levels dose-dependently suppressed ConA-induced IL-2 production. • MelNH2 inhibited the activation of NFAT and NFκB, which control IL-2 expression.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d1d464936fd14de259a844061a4ec2bdTest
https://doi.org/10.1016/j.bbrep.2019.100658Test

المؤلفون: Verena Christen, Magdalena Camenzind, Karl Fent

المصدر: Toxicology Reports, Vol 1, Iss C, Pp 1143-1151 (2014)
Toxicology Reports

مصطلحات موضوعية: MAPK/ERK pathway, Health, Toxicology and Mutagenesis, eIF2α, eukaryotic initiation factor 2α, ATF-4, Activating transcription factor 4, Noxa, phorbol-12-myristate-13-acetate-induced protein 1, Toxicology, CREB, medicine.disease_cause, CHOP, CCAAT/enhancer binding protein-homologous protein, Article, MAPK, mitogen-activated protein kinase signaling pathway, p53, TP53-tumorsuppressor-gene, PERK, protein kinase like ER kinase, XBP-1, X-box binding protein 1, UPR, unfolded protein response, IFN α, interferon α, lcsh:RA1190-1270, NFκB, nuclear factor ‘kappa-light-chain-enhancer’ of activated B-cells, medicine, Protein kinase A, STAT1, signal transducer and activator of transcription 1, lcsh:Toxicology. Poisons, Proinflammatory response, Iinterferon-stimulated genes, biology, SiO2-NPs, silica nanoparticles, Tumor necrosis factor alpha, Endoplasmic reticulum, Human hepatoma cells, BiP, binding immunoglobulin protein, ISGs, interferon stiulated genes, Cell biology, TNFα, tumor necrosis factor α, IRE-1, inositol-requiring protein 1, IFN β, interferon β, ISG-15, interferon-induced 17 kDa protein, Mitogen-activated protein kinase, PP2A, protein phosphatase 2a, Immunology, ATF-6, activating transcription factor 6, biology.protein, Unfolded protein response, CREB, cAMP response element-binding protein, Signal transduction, Huh7, human hepatoma cells, IP-10, interferon gamma-induced protein 10, Oxidative stress, IRF-9, interferon regulatory factor 9

الوصف: Highlights • Silica nanoparticles (225 nm) induced ER stress and unfolded protein response. • MAPK pathway and associated genes are induced. • PP2Ac, TNFα, NFкB and interferon stimulated genes are up-regulated. • p53 is down-regulated, indicating inhibition of apoptosis. • The data suggest hepatotoxic, inflammatory and tumorigenic action of SiO2-NPs.
Application of silica nanoparticles (SiO2-NPs) may result in human exposure. Here we investigate unexplored modes of action by which SiO2-NPs with average size of 225 nm act on human hepatoma cells (Huh7). We focused on the endoplasmic (ER) stress response and on mitogen-activated protein kinase (MAPK) signaling pathways. Both pathways were induced. ER stress and the associated three unfolded protein response (UPR) pathways were activated as demonstrated by significant inductions of BiP and XBP-1s and a moderate but significant induction of ATF-4 at 0.05 and 0.5 mg/ml. In addition to activation of NFкB interferon stimulated genes IP-10, IRF-9, and ISG-15 were up-regulated. As a consequence of ER stress, the pro-inflammatory cytokine TNFα and PP2Ac were induced following exposure to 0.05 mg/ml SiO2-NPs. Additionally, this occurred at 0.005 mg/ml SiO2-NPs for TNFα at 24 h. This in turn led to a strong transcriptional induction of MAP-kinases and its target genes cJun, cMyc and CREB. A strong transcriptional down-regulation of the proapoptotic gene p53 occurred at 0.05 and 0.5 mg/ml SiO2-NP. Exposure of Huh7 cells to the anti-oxidant N-acetyl cysteine reduced transcriptional induction of ER stress markers demonstrating a link between the induction of oxidative stress and ER stress. Our study demonstrates that SiO2-NPs lead to strong ER stress and UPR induction, oxidative stress, activation of MAPK signaling and down-regulation of p53. All of these activated pathways, which are analyzed here for the first time in detail, inhibit apoptosis and induce cell proliferation, which may contribute to a hepatotoxic, inflammatory and tumorigenic action of SiO2-NPs.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c57ecd7b912ae1263fdae8c13fa402bbTest

المؤلفون: Lucy, Yang, Joseph, Cheriyan, David D, Gutterman, Ruth J, Mayer, Zsuzsanna, Ament, Jules L, Griffin, Aili L, Lazaar, David E, Newby, Ruth, Tal-Singer, Ian B, Wilkinson

المصدر: Chest

مصطلحات موضوعية: Adult, Male, Vasodilator Agents, NFκB, nuclear factor kappa light-chain enhancer of activated B cells, LNMMA, NG-monomethyl-L-arginine, smokers, In Vitro Techniques, Bradykinin, Pulmonary Disease, Chronic Obstructive, EDHF, endothelium-derived hyperpolarizing factor, 8,11,14-Eicosatrienoic Acid, endothelial function, EET, epoxyeicosatrienoic acid, Humans, COPD, DHET, dihydroxyepoxyeicosatrienoic acid, Fluconazole, Aged, PAI-1, plasminogen activator inhibitor type 1, Epoxide Hydrolases, Cyclohexylamines, NO, nitric oxide, Triazines, Smoking, LNAME, L-nitroarginine methyl ester, clinical trial, Middle Aged, Overweight, sEH, soluble epoxide hydrolase, Original Research: COPD, tPA, tissue plasminogen activator, Plethysmography, Vasodilation, Forearm, soluble epoxide hydrolase inhibitor, Case-Control Studies, SNP, sodium nitroprusside, Blood Vessels, CYP, cytochrome P450, EC50, half maximal effective concentration, Endothelium, Vascular, EETs

الوصف: Background Smoking and COPD are risk factors for cardiovascular disease, and the pathogenesis may involve endothelial dysfunction. We tested the hypothesis that endothelium-derived epoxyeicosatrienoic acid (EET)-mediated endothelial function is impaired in patients with COPD and that a novel soluble epoxide hydrolase inhibitor, GSK2256294, attenuates EET-mediated endothelial dysfunction in human resistance vessels both in vitro and in vivo. Methods Endogenous and stimulated endothelial release of EETs was assessed in 12 patients with COPD, 11 overweight smokers, and two matched control groups, using forearm plethysmography with intraarterial infusions of fluconazole, bradykinin, and the combination. The effects of GSK2256294 on EET-mediated vasodilation in human resistance arteries were assessed in vitro and in vivo in a phase I clinical trial in healthy overweight smokers. Results Compared with control groups, there was reduced vasodilation with bradykinin (P = .005), a blunted effect of fluconazole on bradykinin-induced vasodilation (P = .03), and a trend toward reduced basal EET/dihydroxyepoxyeicosatrienoic acid ratio in patients with COPD (P = .08). A similar pattern was observed in overweight smokers. In vitro, 10 μM GSK2256294 increased 11,12-EET-mediated vasodilation compared with vehicle (90% ± 4.2% vs 72.6% ± 6.2% maximal dilatation) and shifted the bradykinin half-maximal effective concentration (EC50) (–8.33 ± 0.172 logM vs –8.10 ± 0.118 logM; P = .001 for EC50). In vivo, 18 mg GSK2256294 improved the maximum bradykinin response from 338% ± 46% before a dose to 566% ± 110% after a single dose (P = .02) and to 503% ± 123% after a chronic dose (P = .003). Conclusions GSK2256294 attenuates smoking-related EET-mediated endothelial dysfunction, suggesting potential therapeutic benefits in patients with COPD. Trial Registry ClinicalTrials.gov; No.: NCT01762774; URL: www.clinicaltrials.gov

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::057e7d0cabc13f538b80989266ad2f46Test
https://pubmed.ncbi.nlm.nih.gov/27884766Test