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IFN-gamma signaling

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https://www.readbyqxmd.com/read/28904198/type-1-interferon-signalling-to-dendritic-cells-limits-murid-herpesvirus-4-spread-from-the-olfactory-epithelium
#1
Clara Lawler, Philip G Stevenson
Murid Herpesvirus-4 (MuHV-4) is a B cell-tropic gamma-herpesvirus that can be studied in vivo Despite viral evasion, type 1 interferons (IFN-I) limit its spread. After MuHV-4 inoculation into footpads, IFN-I protect lymph node subcapsular sinus macrophages (SSM) against productive infection; after peritoneal inoculation, they protect splenic marginal zone macrophages; and they limit MuHV-4 replication in the lungs. While invasive infections can test specific aspects of host colonization, it is important also to understand natural infection...
September 13, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28883123/post-translational-modification-of-the-interferon-gamma-receptor-alters-its-stability-and-signaling
#2
James D Londino, Dexter L Gullick, Travis B Lear, Tomeka L Suber, Nathaniel M Weathington, Luke S Masa, Bill B Chen, Rama K Mallampalli
The IFN gamma receptor 1 (IFNGR1) binds IFN gamma and activates gene transcription pathways crucial for controlling bacterial and viral infections. Although decreases in IFNGR1 surface levels have been demonstrated to inhibit IFN gamma signaling, little is known regarding the molecular mechanisms controlling receptor stability. Here we show in epithelial and monocytic cell lines that IFNGR1 displays K48 polyubiquitination, is proteasomally degraded, and harbors three ubiquitin acceptor sites at K277, K279, and K285...
September 7, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28879548/cepharanthine-inhibits-ifn-%C3%AE-induced-cxcl10-by-suppressing-the-jak2-stat1-signal-pathway-in-human-salivary-gland-ductal-cells
#3
Keiko Aota, Tomoko Yamanoi, Koichi Kani, Masayuki Azuma
Cepharanthine, a biscolaurine alkaloid isolated from the plant Stephania cephalantha Hayata, has been reported to have potent anti-inflammatory properties. Here, we investigated the effects of cepharanthine on the expression of CXCL10 (a CXC chemokine induced by interferon-gamma [IFN-γ] that has been observed in a wide variety of chronic inflammatory disorders and autoimmune conditions) in IFN-γ-treated human salivary gland cell lines. We observed that IFN-γ-induced CXCL10 production in NS-SV-DC cells (a human salivary gland ductal cell line), but not in NS-SV-AC cells (a human salivary gland acinar cell line)...
September 6, 2017: Inflammation
https://www.readbyqxmd.com/read/28870857/molecular-characterization-and-expression-analysis-of-interferon-gamma-in-black-seabream-acanthopagrus-schlegelii
#4
Yangxi Xiang, Wei Liu, Peng Jia, Yunlong Li, Yilin Jin, Limin Chen, Jing Zhang, Kuntong Jia, Meisheng Yi
Interferon gamma (IFN-γ) is a major component in immunological signaling and plays a key role in resisting viral infection. In this study, we identified and characterized an IFN-γ gene (AsIFN-γ) in the marine fish black seabream (Acanthopagrus schlegelii). We cloned AsIFN-γ genomic sequence, which comprises four exons, three introns and an upstream promoter including several conserved regulatory elements. The complete cDNA of AsIFN-γ was 816 bp in length and encoded a putative 194 amino acids (aa) protein with a 22 aa signal peptide, six α-helices and one nuclear localization signal (NLS)...
September 7, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28860618/interferon-gamma-regulates-inflammatory-cell-death-by-targeting-necroptosis-in-experimental-autoimmune-arthritis
#5
Seung Hoon Lee, Ji Ye Kwon, Se-Young Kim, KyoungAh Jung, Mi-La Cho
Interferon γ (IFN-γ) induces an inflammatory response and apoptotic cell death. Rheumatoid arthritis (RA) is a systemic inflammatory disease associated with increased levels of inflammatory mediators, including tumour necrosis factor α (TNF-α) and T helper (Th) 17 cells, and downregulation of apoptosis of inflammatory cells. We hypothesized that IFN-γ would reduce inflammatory cell death in vitro and that loss of IFN-γ would aggravate inflammation in vivo. IFN-γ downregulated necroptosis and the expression of cellular FLICE-like inhibitory protein (cFLIPL) and mixed lineage kinase domain-like (MLKL)...
August 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28843559/an-amplified-fluorescent-aptasensor-based-on-single-stranded-dna-binding-protein-copper-and-silica-nanoparticles-for-sensitive-detection-of-interferon-gamma
#6
Seyed Mohammad Taghdisi, Noor Mohammad Danesh, Mohammad Ramezani, Rezvan Yazdian-Robati, Khalil Abnous
It is great significance to identify interferon-gamma (IFN-γ), as a biological marker for diagnosis of latent tuberculosis, in serum samples. In this paper, a novel fluorescent aptasensor was fabricated and applied for sensitive and specific detection of IFN-γ. This biosensor was based on hairpin structure of oligonucleotide, single-stranded DNA-binding protein (SSB), copper nanoparticles (CuNPs) and silica nanoparticles coated with streptavidin (SNPs-Streptavidin). The presences of double-stranded DNA (dsDNA) region and poly thymine (T) in the hairpin structure of the oligonucleotide, SSB and SNPs-streptavidin caused IFN-γ determination with high selectivity and sensitivity...
September 1, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/28838042/the-role-of-infiltrating-immune-cells-in-dysfunctional-adipose-tissue
#7
Tomasz J Guzik, Dominik S Skiba, Rhian M Touyz, David G Harrison
Adipose tissue (AT) dysfunction, characterized by loss of its homeostatic functions, is a hallmark of non-communicable diseases. It is characterized by chronic low-grade inflammation and is observed in obesity, metabolic disorders such as insulin resistance and diabetes. While classically it has been identified by increased cytokine or chemokine expression, such as increased MCP-1, RANTES, IL-6, interferon (IFN) gamma or TNFα, mechanistically, immune cell infiltration is a prominent feature of the dysfunctional AT...
July 1, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28828860/potential-resolved-electrochemiluminescence-for-simultaneous-determination-of-triple-latent-tuberculosis-infection-markers
#8
Bin Zhou, Mingyao Zhu, Yan Hao, Peihui Yang
A novel electrochemiluminescence (ECL) immunosensor based on the potential-resolved strategy was first developed for simultaneous determination of triple latent tuberculosis infection (LTBI) markers with high sensitivity, interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and interleukin (IL)-2. In this work, luminol and self-prepared carbon quantum dots and CdS quantum dots were integrated onto gold nanoparticles and magnetic beads in sequence to fabricate potential-resolved ECL nanoprobes with signal amplification...
September 13, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28819304/novel-stat-binding-elements-mediate-il-6-regulation-of-mmp-1-and-mmp-3
#9
Samuel J Cutler, James D Doecke, Ibtisam Ghazawi, Jinbo Yang, Lyn R Griffiths, Kevin J Spring, Stephen J Ralph, Albert S Mellick
Dynamic remodelling of the extracellular matrix (ECM) is a key feature of cancer progression. Enzymes that modify the ECM, such as matrix metalloproteinases (MMPs), have long been recognised as important targets of anticancer therapy. Inflammatory cytokines are known to play a key role in regulating protease expression in cancer. Here we describe the identification of gamma-activated site (GAS)-like, signal transducer and activator of transcription (STAT) binding elements (SBEs) within the proximal promoters of the MMP-1 and MMP-3 genes, which in association with AP-1 components (c-Fos or Jun), bind STAT-1 in a homodimer like complex (HDLC)...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28742217/the-inflammatory-cytokine-interferon-gamma-inhibits-sortilin-1-expression-in-hepatocytes-via-the-jak-stat-pathway
#10
John Pirault, Konstantinos A Polyzos, Marcelo H Petri, Daniel Fj Ketelhuth, Magnus Bäck, Göran K Hansson
Sortilin-1, a receptor of the VPS10p family, has been associated with cardiovascular disease in genome-wide association studies. It is implicated in lipoprotein metabolism, secretion of proprotein convertase subtilisin/kexin type 9 (PCSK9) and secretion of inflammatory cytokines. However, its own regulation remains unclear. Chronic inflammation is a hallmark of atherosclerosis and absence of regulatory T (Treg) cells is associated with reduced protein expression of sortilin-1 in the liver. Therefore, we postulated that mediator(s) of inflammation known to be downregulated by regulatory T cells may modulate sortilin-1 expression...
July 25, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28736298/calcitriol-mediated-reduction-in-ifn-%C3%AE-output-in-t-cell-large-granular-lymphocytic-leukemia-requires-vitamin-d-receptor-upregulation
#11
M Paige Kulling, C Kristine Olson, L Thomas Olson, E Cait Hamele, N Kathryn Carter, J David Feith, P Thomas Loughran
Constitutively activated STAT1 and elevated IFN-γ are both characteristic of T cell large granular lymphocytic leukemia (T-LGLL), a rare incurable leukemia with clonal expansion of cytotoxic T cells due to defective apoptosis. Interferon gamma (IFN-γ) is an inflammatory cytokine that correlates with worse progression and symptomology in multiple autoimmune diseases and cancers. In canonical IFN-γ-STAT1 signaling, IFN-γ activates STAT1, a transcription factor, via phosphorylation of tyrosine residue 701 (p-STAT1)...
July 20, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28723140/rapid-and-label-free-detection-of-interferon-gamma-via-an-electrochemical-aptasensor-comprising-a-ternary-surface-monolayer-on-a-gold-interdigitated-electrode-array
#12
Shaowei Ding, Curtis Mosher, Xian Y Lee, Suprem R Das, Allison A Cargill, Xiaohui Tang, Bolin Chen, Eric S McLamore, Carmen Gomes, Jesse M Hostetter, Jonathan C Claussen
A label-free electrochemical impedance spectroscopy (EIS) aptasensor for rapid detection (<35 min) of interferon-gamma (IFN-γ) was fabricated by immobilizing a RNA aptamer capture probe (ACP), selective to IFN-γ, on a gold interdigitated electrode array (Au IDE). The ACP was modified with a thiol group at the 5' terminal end and subsequently co-immobilized with 1,6-hexanedithiol (HDT) and 6-mercapto-1-hexanolphosphate (MCH) to the gold surface through thiol-gold interactions. This ACP/HDT-MCH ternary surface monolayer facilitates efficient hybridization with IFN-γ and displays high resistance to nonspecific adsorption of nontarget proteins [i...
February 24, 2017: ACS Sensors
https://www.readbyqxmd.com/read/28680742/modulation-of-mhc-class-i-surface-expression-in-b16f10-melanoma-cells-by-methylseleninic-acid
#13
Claudia Lennicke, Jette Rahn, Jürgen Bukur, Falko Hochgräfe, Ludger A Wessjohann, Rudolf Lichtenfels, Barbara Seliger
The essential trace element selenium (Se) might play a role in cancer prevention as well as for cancer therapy. Its metabolite methylselenol is able to kill cells through distinct mechanisms including induction of reactive oxygen species, DNA damage and apoptosis. Since methylselenol affects innate immune responses by modulating the expression of NKG2D ligands, the aim of this study was to determine whether the methylselenol generating compound methylseleninic acid (MSA) influences the expression of the MHC class I surface antigens and growth properties thereby reverting immune escape...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28667090/lentiviral-vectors-escape-innate-sensing-but-trigger-p53-in-human-hematopoietic-stem-and-progenitor-cells
#14
Francesco Piras, Michela Riba, Carolina Petrillo, Dejan Lazarevic, Ivan Cuccovillo, Sara Bartolaccini, Elia Stupka, Bernhard Gentner, Davide Cittaro, Luigi Naldini, Anna Kajaste-Rudnitski
Clinical application of lentiviral vector (LV)-based hematopoietic stem and progenitor cells (HSPC) gene therapy is rapidly becoming a reality. Nevertheless, LV-mediated signaling and its potential functional consequences on HSPC biology remain poorly understood. We unravel here a remarkably limited impact of LV on the HSPC transcriptional landscape. LV escaped innate immune sensing that instead led to robust IFN responses upon transduction with a gamma-retroviral vector. However, reverse-transcribed LV DNA did trigger p53 signaling, activated also by non-integrating Adeno-associated vector, ultimately leading to lower cell recovery ex vivo and engraftment in vivo These effects were more pronounced in the short-term repopulating cells while long-term HSC frequencies remained unaffected...
September 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28630063/listeria-vectored-vaccine-expressing-the-mycobacterium-tuberculosis-30-kda-major-secretory-protein-via-the-constitutively-active-prfa-regulon-boosts-bcg-efficacy-against-tuberculosis
#15
Qingmei Jia, Barbara Jane Dillon, Saša Masleša-Galić, Marcus A Horwitz
A potent vaccine against tuberculosis, one of the world's deadliest diseases, is needed to enhance the immunity of people worldwide, most of whom have been vaccinated with the partially effective BCG vaccine. Here we investigate novel live attenuated recombinant Listeria monocytogenes (rLm) vaccines expressing the Mycobacterium tuberculosis (Mtb) 30 kDa major secretory protein (r30/Ag85B) (rLm30) as heterologous booster vaccines in animals primed with BCG. Using three attenuated Lm vectors, rLm ΔactA (LmI), rLm ΔactA ΔinlB (LmII), and rLm ΔactA ΔinlBprfA* (LmIII), we constructed five rLm30 vaccine candidates expressing the r30 linked in-frame to the Lm Listeriolycin O signal sequence and driven by the hly promoter (h30) or linked in-frame to the ActA N-terminus and driven by the actA promoter (a30)...
June 19, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28623917/the-dynamic-changes-of-interferon-lambdas-related-genes-and-proteins-in-jak-stat-pathway-in-both-acute-and-chronic-hiv-1-infected-patients
#16
Guoxian Zhao, Lifeng Liu, Bin Su, Tong Zhang, Peng Chen, Wei Li, Hao Wu
BACKGROUND: Host immune responses during acute HIV-1 infection can influence the viral setpoint, which is a predictor of disease progression. Interferon (IFN)-lambdas are newly classified type III interferons, which use JAK-STAT pathway. Currently, the dynamics of IFN-lambdas related genes and proteins expression in the signaling pathway have not been well elaborated, especially in acute HIV-1-infected patients. OBJECTIVES: To evaluate the dynamic changes of IFN-lambdas related genes and proteins in JAK/STAT pathway in acute HIV-1-infected patients, and analyze their correlation with CD4 T cell counts and HIV-1 viral loads...
June 17, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28610842/fumigaclavine-c-exhibits-anti-inflammatory-effects-by-suppressing-high-mobility-group-box-protein-1-relocation-and-release
#17
Wanguo Yu, Zhenghua Pan, Yixiang Zhu, Faliang An, Yanhua Lu
A previous study demonstrated that Fumigaclavine C (FC) had a potential immunosuppressive activity against concanavalin A-induced hepatitis in mice. However, the precise mechanisms of the anti-inflammatory and hepatoprotective effects of FC are incompletely delineated. This study further investigated the protective effects of FC on lipopolysaccharide (LPS)-induced murine RAW264.7 cells and the underlying molecular mechanism in liver kupffer cells. FC differentially attenuated the production of tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interferon gamma (IFN-γ), and high mobility group box protein 1 (HMGB-1)...
June 10, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28606480/sphingosine-kinase-2-in-autoimmune-inflammatory-disease-and-the-development-of-sphingosine-kinase-2-inhibitors
#18
REVIEW
Nigel J Pyne, David R Adams, Susan Pyne
The purpose of this Opinion is to present a case for targeting sphingosine kinase 2 (SK2) in autoimmune/inflammatory disease. Data obtained using Sphk2(-/-) mice suggest that SK2 is an anti-inflammatory enzyme, although this might be misleading because of a compensatory increase in the expression of a second isoform, sphingosine kinase 1 (SK1), which functions as a proinflammatory enzyme. SK2 is involved in regulating interleukin (IL)-12/interferon gamma (IFN-γ) and histone deacetylase-1/2 (HDAC-1/2) signalling and, potentially, retinoid-related orphan receptor gamma t (ROR-γt) stability linked with T helper (Th) 17 cell polarisation...
June 9, 2017: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/28561280/anti-fc%C3%AE-riib-cd32-antibodies-differentially-modulate-murine-fviii-specific-recall-response-in%C3%A2-vitro
#19
N Vollack, J Friese, S Bergmann, M S Cragg, A Tiede, S Werwitzke
Fc gamma receptors (FcγRs) for IgG regulate adaptive immune responses by modulating activating and inhibitory signalling pathways within immune cells. Data from a haemophilia A mouse model demonstrate that genetic deletion or blockade of the inhibitory FcγR (CD32) suppresses the formation of antibody-secreting cells (ASCs) in vitro. Mechanisms preventing the FVIII-specific recall response, however, remain unclear. Here, the potential role of CD32 inhibition was studied by differentially modulating receptor activity with selected anti-CD32 monoclonal antibodies (mAbs)...
August 2017: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/28519900/type-i-interferon-pathway-in-cns-homeostasis-and-neurological-disorders
#20
REVIEW
Thomas Blank, Marco Prinz
Type I interferons (IFNs), IFN-α and IFN-β, represent the major effector cytokines of the host immune response against viruses and other intracellular pathogens. These cytokines are produced via activation of numerous pattern recognition receptors, including the Toll-like receptor signaling network, retinoic acid-inducible gene-1 (RIG-1), melanoma differentiation-associated protein-5 (MDA-5) and interferon gamma-inducible protein-16 (IFI-16). Whilst the contribution of type I IFNs to peripheral immunity is well documented, they can also be produced by almost every cell in the central nervous system (CNS)...
September 2017: Glia
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