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Type 3 Interferon

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https://www.readbyqxmd.com/read/28808967/purification-of-cyclic-gmp-amp-from-viruses-and-measurement-of-its-activity-in-cell-culture
#1
Alice Mayer, Jonathan Maelfait, Anne Bridgeman, Jan Rehwinkel
Sensing of cytoplasmic DNA by cGAS is essential for the initiation of immune responses against several viruses. cGAS also plays important roles in some autoinflammatory and autoimmune diseases and may be involved in immune responses targeting cancer cells. Once activated, cGAS catalyzes the formation of the di-nucleotide 2'-3'-cyclic GMP-AMP (cGAMP), which propagates a signaling cascade leading to the production of type I interferons (IFNs). Interestingly, cGAMP is incorporated into enveloped viruses and is transferred to newly infected cells by virions...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28807907/an-original-chemical-series-of-pyrimidine-biosynthesis-inhibitors-that-boost-the-antiviral-interferon-response
#2
Marianne Lucas-Hourani, Daniel Dauzonne, Hélène Munier-Lehmann, Samira Khiar, Sébastien Nisole, Julien Dairou, Olivier Helynck, Philippe V Afonso, Frédéric Tangy, Pierre-Olivier Vidalain
De novo pyrimidine biosynthesis is a key metabolic pathway involved in multiple biosynthetic processes. Here, we identified an original series of 3-(1H-indol-3-yl)-2,3-dihydro-4H-furo[3,2-c]chromen-4-one derivatives as a new class of pyrimidine biosynthesis inhibitors formed by two edge-fused polycyclic moieties. We show that identified compounds exhibit a broad-spectrum antiviral activity as well as immunostimulatory properties, in line with recent reports linking de novo pyrimidine biosynthesis with innate defense mechanisms against viruses...
August 14, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28807557/the-role-of-toll-like-receptor-3-in-chronic-contact-hypersensitivity-induced-by-repeated-elicitation
#3
Risa Yasuike, Risa Tamagawa-Mineoka, Mayumi Ueta, Naomi Nakamura, Shigeru Kinoshita, Norito Katoh
BACKGROUND: Accumulating evidence suggests that Toll-like receptor (TLR)-3 signaling is involved in non-infectious immune and inflammatory reactions as well as in viral infections. The skin of patients with atopic dermatitis (AD) is often infected with virus and bacteria, leading to the aggravation of atopic symptoms. These findings suggest TLR3 signaling may be involved in the pathogenesis of AD, but the exact role of TLR3 in AD remains to be defined. OBJECTIVE: The purpose of this study was to investigate the role of TLR3 in chronic contact hypersensitivity reactions induced by repeated elicitation, resembling the features of AD...
August 4, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/28803068/improved-therapeutic-efficacy-of-mammalian-expressed-recombinant-interferon-gamma-against-ovarian-cancer-cells
#4
Ali Razaghi, Carina Villacrés, Vincent Jung, Narges Mashkour, Michael Butler, Leigh Owens, Kirsten Heimann
Human interferon gamma (hIFNγ) affects tumour cells and modulates immune responses, showing promise as an anti-cancer biotherapeutic. This study investigated the effect of glycosylation and expression system of recombinant hIFNγ in ovarian carcinoma cell lines, PEO1 and SKOV3. The efficacy of E. coli- and mammalian-expressed hIFNγ (hIFNγ-CHO and HEK293, glycosylated/de-glycosylated) on cytostasis, cell death (MTT, and Guava-ViaCount(®) flow-cytometry) and apoptotic signalling (Western blot of Cdk2, histone H3, procaspase-3, FADD, cleaved PARP, and caspase-3) was examined...
August 9, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28802876/hepatocellular-carcinoma-risk-following-direct-acting-antiviral-hcv-therapy-a-systematic-review-meta-analyses-and-meta-regression
#5
Reem Waziry, Behzad Hajarizadeh, Jason Grebely, Janaki Amin, Matthew Law, Mark Danta, Jacob George, Gregory J Dore
BACKGROUND: Risk of hepatocellular carcinoma (HCC) occurrence or recurrence following direct-acting antiviral (DAA) HCV therapy remains unclear. The aims of this study were: 1) In patients with HCV-related cirrhosis, to compare the rate of HCC occurrence following DAA versus interferon (IFN)-based cure, and; 2) In patients who received curative HCC treatment, to compare rate of HCC recurrence following DAA versus IFN-based cure. METHODS: A search was conducted for reports published between January 2000 and February 2017...
August 9, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28796422/insulin-producing-cells-derived-from-induced-pluripotent-stem-cells-of-patients-with-fulminant-type-1-diabetes-vulnerability-to-cytokine-insults-and-increased-expression-of-apoptosis-related-genes
#6
Yoshiya Hosokawa, Taro Toyoda, Kenji Fukui, Megu Yamaguchi Baden, Michinori Funato, Yasushi Kondo, Tomomi Sudo, Hiromi Iwahashi, Marina Kishida, Chihiro Okada, Akira Watanabe, Isao Asaka, Kenji Osafune, Akihisa Imagawa, Iichiro Shimomura
AIMS/INTRODUCTION: This study was performed to generate induced pluripotent stem cells (iPSCs) from patients with fulminant type 1 diabetes (FT1D) and evaluate the cytokine-induced apoptotic reactions of beta-like insulin-producing cells differentiated from the iPSCs. MATERIALS AND METHODS: iPSCs were generated from fibroblasts of patients with FT1D by inducing six reprogramming factors. Insulin-producing cells were differentiated from the iPSCs in vitro. The proportion of cleaved caspase-3-positive or TUNEL-positive cells among INSULIN (INS)-positive cells derived from FT1D-iPSC and control human-iPSC lines was evaluated under treatment with tumor necrosis factor-alpha, interleuin-1-beta, and interferon-gamma...
August 10, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28769107/innate-immune-basis-for-rift-valley-fever-susceptibility-in-mouse-models
#7
Rashida Lathan, Dominique Simon-Chazottes, Grégory Jouvion, Ophélie Godon, Marie Malissen, Marie Flamand, Pierre Bruhns, Jean-Jacques Panthier
Rift Valley fever virus (RVFV) leads to varied clinical manifestations in animals and in humans that range from moderate fever to fatal illness, suggesting that host immune responses are important determinants of the disease severity. We investigated the immune basis for the extreme susceptibility of MBT/Pas mice that die with mild to acute hepatitis by day 3 post-infection compared to more resistant BALB/cByJ mice that survive up to a week longer. Lower levels of neutrophils observed in the bone marrow and blood of infected MBT/Pas mice are unlikely to be causative of increased RVFV susceptibility as constitutive neutropenia in specific mutant mice did not change survival outcome...
August 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28768867/mechanism-of-interferon-stimulated-gene-induction-in-hiv-1-infected-macrophages
#8
Najla Nasr, Abdullateef A Alshehri, Thomas K Wright, Maryam Shahid, Bonnie M Heiner, Andrew N Harman, Rachel A Botting, Karla J Helbig, Michael R Beard, Kazuo Suzuki, Anthony D Kelleher, Paul Hertzog, Anthony L Cunningham
Viruses manipulate the complex interferon and interferon stimulated gene (ISG) system in different ways. We have previously shown that HIV inhibits type I and III interferons in its key target cells but directly stimulates a subset of >20 ISGs in macrophages and dendritic cells many of which are antiviral. Here we examined the mechanism of induction of ISGs and showed this occurred in two phases. The first phase was transient (0-24hpi) induced mainly by extracellular vesicles, and one of its component proteins HSP90α, contained within the HIV inoculum...
August 2, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28765956/anti-cd20-monoclonal-antibody-combined-with-adenovirus-vector-mediated-il-10-regulates-spleen-cd4-cd8-t%C3%A2-cells-and-t-bet-gata-3-expression-in-nod-mice
#9
Aiping Tang, Cheng Li, Zhihong Chen, Tang Li
Type 1 diabetes (T1D) is an autoimmune disease characterized by a selective destruction of insulin-secreting β-cells. Both T cells and B cells serve a crucial role in pathogenesis and development of T1D. CD20 is a specific membrane antigen of B lymphocytes, while interleukin (IL)‑10 is an important cytokine secreted by T helper 2 cells and has a short half‑life in vivo. The combined effect of anti‑CD20 and IL‑10 on immune function of mice with T1D remains unknown. In the present study, 30 non‑obese diabetic (NOD) mice were treated with anti‑CD20 and adenoviral vector‑mediated interleukin‑10 (Ad‑mIL‑10) therapy...
July 28, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28753407/il-29-enhances-cxcl10-production-in-tnf-%C3%AE-stimulated-human-oral-epithelial-cells
#10
Yoshitaka Hosokawa, Ikuko Hosokawa, Satoru Shindo, Kazumi Ozaki, Takashi Matsuo
Interleukin-29 (IL-29) is a cytokine belonging to the Type III interferon family. It was recently detected in the gingival crevicular fluid of periodontitis patients. However, the role of IL-29 in the pathogenesis of periodontal disease remains unknown. The aim of this study was to examine the effects of IL-29 on C-X-C motif chemokine ligand 10 (CXCL10) production in human oral epithelial cells. We measured CXCL10 production in TR146 cells, which is a human oral epithelial cell line, using an enzyme-linked immunosorbent assay...
August 2017: Immunological Investigations
https://www.readbyqxmd.com/read/28750037/generation-and-characterization-of-interferon-lambda-1-resistant-h1n1-influenza-a-viruses
#11
Natalia A Ilyushina, Vladimir Y Lugovtsev, Anastasia P Samsonova, Faruk G Sheikh, Nicolai V Bovin, Raymond P Donnelly
Influenza A viruses pose a constant potential threat to human health. In view of the innate antiviral activity of interferons (IFNs) and their potential use as anti-influenza agents, it is important to know whether viral resistance to these antiviral proteins can arise. To examine the likelihood of emergence of IFN-λ1-resistant H1N1 variants, we serially passaged the A/California/04/09 (H1N1) strain in a human lung epithelial cell line (Calu-3) in the presence of increasing concentrations of recombinant IFN-λ1 protein...
2017: PloS One
https://www.readbyqxmd.com/read/28746799/lack-of-il-6-in-the-tumor-microenvironment-augments-type-1-immunity-and-increases-the-efficacy-of-cancer-immunotherapy
#12
Yosuke Ohno, Yujiro Toyoshima, Hideaki Yurino, Norikazu Monma, Huihui Xiang, Kentaro Sumida, Shun Kaneumi, Satoshi Terada, Shinichi Hashimoto, Kazuho Ikeo, Shigenori Homma, Hideki Kawamura, Norihiko Takahashi, Akinobu Taketomi, Hidemitsu Kitamura
Conquering immunosuppression in tumor microenvironments is crucial for effective cancer immunotherapy. It is well known that interleukin (IL)-6, a pleiotropic cytokine, is produced in the tumor-bearing state. In this study, we investigated the precise effects of IL-6 on antitumor immunity and the subsequent tumorigenesis in tumor-bearing hosts. CT26 cells, a murine colon cancer cell line, were intradermally injected into wild-type and IL-6-deficient mice. As a result, we found that tumor growth was decreased significantly in IL-6-deficient mice compared with wild-type mice and the reduction was abrogated by depletion of CD8(+) T cells...
July 26, 2017: Cancer Science
https://www.readbyqxmd.com/read/28739436/efficacy-of-isoniazid-salvage-therapy-for-latent-tuberculosis-infection-in-patients-with-immune-mediated-inflammatory-disorders-a-retrospective-cohort-study-in-taiwan
#13
Shiang-Fen Huang, Ming-Han Chen, Fu-Der Wang, Chang-Youh Tsai, Chang-Phone Fung, Wei-Juin Su
BACKGROUND: Active tuberculosis (TB) in patients with latent tuberculosis infection (LTBI) was associated with use of biological agents for immune-mediated inflammatory disorders (IMIDs). For decreasing active TB, isoniazid prophylaxis therapy was administered before biologic therapy among IMID patients with LTBI. However, for patients who had been received biologics for a long time with unknown status of LTBI or exposure history of active TB, the prevalence of LTBI and efficacy of isoniazid therapy were unclear...
June 29, 2017: Journal of Microbiology, Immunology, and Infection, Wei Mian Yu Gan Ran za Zhi
https://www.readbyqxmd.com/read/28738877/unexpected-complexity-in-the-interference-activity-of-a-cloned-influenza-defective-interfering-rna
#14
Bo Meng, Kirsten Bentley, Anthony C Marriott, Paul D Scott, Nigel J Dimmock, Andrew J Easton
BACKGROUND: Defective interfering (DI) viruses are natural antivirals made by nearly all viruses. They have a highly deleted genome (thus being non-infectious) and interfere with the replication of genetically related infectious viruses. We have produced the first potential therapeutic DI virus for the clinic by cloning an influenza A DI RNA (1/244) which was derived naturally from genome segment 1. This is highly effective in vivo, and has unexpectedly broad-spectrum activity with two different modes of action: inhibiting influenza A viruses through RNA interference, and all other (interferon-sensitive) respiratory viruses through stimulating interferon type I...
July 24, 2017: Virology Journal
https://www.readbyqxmd.com/read/28737923/cosilencing-intestinal-transglutaminase-2-and-interleukin-15-using-gelatin-based-nanoparticles-in-an-in-vitro-model-of-celiac-disease
#15
Husain Attarwala, Valerie Clausen, Prasoon Chaturvedi, Mansoor M Amiji
In this study, we have developed a type B gelatin nanoparticle based siRNA delivery system for silencing of intestinal transglutaminase-2 (TG2) and interleukin-15 (IL-15) genes in cultured human intestinal epithelial cells (Caco-2) and murine alveolar macrophage cells (J774A.1). Small interfering RNA (siRNA) targeting the TG2 or IL-15 gene was encapsulated within gelatin nanoparticles using ethanol-water solvent displacement method. Size, charge, and morphology of gelatin nanoparticles were evaluated using a Zetasizer instrument and transmission electron microscopy...
August 10, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28736121/potential-of-circulatory-procalcitonin-as-a-biomarker-reflecting-inflammation-among-south-indian-diabetic-foot-ulcers
#16
Dhamodharan Umapathy, Sireesh Dornadula, Arvind Rajagopalan, Narayana Murthy, Vairamani Mariappanadar, Rajesh Kesavan, Ramkumar Kunka Mohanram
OBJECTIVE: Diabetic foot ulcer (DFU), the major complication associated with diabetes mellitus, has been shown to precede amputation in up to 90% of cases. Recent data reveal that procalcitonin (PCT) is a valid marker for the diagnosis of bacterial infections compared with traditional markers like white blood cell count, C-reactive protein levels, and erythrocyte sedimentation rate in DFU patients. Furthermore, cytokines are proposed to act as modulators and mediators for the expression and release of PCT into the circulation...
July 20, 2017: Journal of Vascular Surgery
https://www.readbyqxmd.com/read/28733891/consequences-of-bisphenol-a-perinatal-exposure-on-immune-responses-and-gut-barrier-function-in-mice
#17
Yann Malaisé, Sandrine Ménard, Christel Cartier, Corinne Lencina, Caroline Sommer, Eric Gaultier, Eric Houdeau, Laurence Guzylack-Piriou
The potent immunomodulatory effect of the endocrine disruptor bisphenol A during development and consequences during life span are of increasing concern. Particular interests have been raised from animal studies regarding the risk of developing food intolerance and infection. We aimed to identify immune disorders in mice triggered by perinatal exposure to bisphenol A. Gravid mice were orally exposed to bisphenol (50 μg/kg body weight/day) from day 15 of pregnancy until weaning. Gut barrier function, local and systemic immunity were assessed in adult female offspring...
July 21, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28733564/the-clinical-features-and-treatment-outcome-of-chronic-hepatitis-c-with-pegylated-interferon-and-ribavirin-in-routine-care
#18
S S Tan, Z Adlin Nadia
AIM: To describe the clinical characteristic of hepatitis C (HCV) patients and the results of pegylated interferon and ribavirin (PegIFN/RBV) therapy in a routine clinical practice. METHODS: A retrospective review of consecutive HCV patients treated with PegIFN/RBV in 2004 to 2012. RESULTS: A total of 273 patients received treatment. The mean age was 44.16 ± 10.5 years and 76% were male. The top 2 self-reported risks were blood or blood product transfusion before 1994 and injection drug use, found in 57...
June 2017: Medical Journal of Malaysia
https://www.readbyqxmd.com/read/28724761/isg15-modulates-type-i-interferon-signaling-and-antiviral-response-during-hepatitis-e-virus-replication
#19
Harini Sooryanarain, Adam J Rogers, Dianjun Cao, Mary Etna R Haac, Yogesh A Karpe, Xiang-Jin Meng
Hepatitis E virus (HEV), a single-stranded positive-sense RNA virus, generally causes a self-limiting acute viral hepatitis, although chronic HEV infection has recently become a significant clinical problem in immunocompromised individuals especially in solid organ transplant recipients. Innate immunity, via type-I interferon (IFN) response, plays an important role during initial stages of a viral infection. ISG15, an IFN-induced ubiquitin-like protein, is known to have an immunomodulatory role, as well as can impart a direct antiviral effect against a wide spectrum of virus families...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28719617/microrna-155-deficiency-leads-to-decreased-autoantibody-levels-and-reduced-severity-of-nephritis-and-pneumonitis-in-pristane-induced-lupus
#20
Harald Leiss, Wilhelm Salzberger, Barbara Jacobs, Irina Gessl, Nicolas Kozakowski, Stephan Blüml, Antonia Puchner, Attila Kiss, Bruno K Podesser, Josef S Smolen, Georg H Stummvoll
OBJECTIVE: We herein examine the role of endogenous miR155 in the development of systemic manifestations in pristane induced lupus. MATERIALS AND METHODS: Systemic lupus in miR155-deficient and wild type mice was induced upon injection of pristane and analyzed after 8 months, PBS-injected mice served as controls. Glomerulonephritis and pneumonitis were quantified using the kidney biopsy score and a newly adapted histomorphometric image analysis system; lung tissue was further analyzed by tissue cytometry...
2017: PloS One
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