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https://www.readbyqxmd.com/read/28748479/sting-signaling-in-cancer-cells-important-or-not
#1
REVIEW
Olga Sokolowska, Dominika Nowis
Stimulator of interferon genes (STING) is an adaptor protein that plays an important role in the activation of type I interferons in response to cytosolic nucleic acid ligands. Recent evidence indicates involvement of the STING pathway in the induction of antitumor immune response. Therefore, STING agonists are now being extensively developed as a new class of cancer therapeutics. However, little is known about the consequences of activated STING-mediated signaling in cancer cells on the efficacy of the antitumor treatment...
July 26, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/28747868/protective-effect-of-momordica-charantia-water-extract-against-liver-injury-in-restraint-stressed-mice-and-the-underlying-mechanism
#2
Yuanyuan Deng, Qin Tang, Yan Zhang, Ruifen Zhang, Zhencheng Wei, Xiaojun Tang, Mingwei Zhang
Background: Momordica charantia is used in China for its jianghuo (heat-clearing and detoxifying) effects. The concept of shanghuo (the antonym of jianghuo, excessive internal heat) in traditional Chinese medicine is considered a type of stress response of the body. The stress process involves internal organs, especially the liver. Objective: We hypothesized that Momordica charantia water extract (MWE) has a hepatoprotective effect and can protect the body from stress. The aim of this study was to investigate the possible effects of MWE against liver injury in restraint-stressed mice...
2017: Food & Nutrition Research
https://www.readbyqxmd.com/read/28747493/role-of-viral-hemorrhagic-septicemia-virus-matrix-m-protein-in-suppressing-host-transcription
#3
Qi Ke, Wade Weaver, Adam Pore, Bartolomeo Gorgoglione, Julia Halo Wildschutte, Peng Xiao, Brian S Shepherd, Allyn Spear, Krishnamurthy Malathi, Carol A Stepien, Vikram N Vakharia, Douglas W Leaman
Viral Hemorrhagic Septicemia virus (VHSV) is a pathogenic fish rhabdovirus found in discrete locales throughout the northern hemisphere. VHSV infection of fish cells leads to upregulation of the host's virus detection response, but the virus quickly suppresses interferon (IFN) production and antiviral genes expression. By systematically screening each of the six VHSV structural and nonstructural genes, we have identified matrix protein (M) as its most potent anti-host protein. VHSV-IVb M alone suppressed mitochondrial antiviral signaling protein (MAVS) and type I IFN-induced gene expression in a dose-dependent manner...
July 26, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28747383/ischemia-reperfusion-induces-interferon-stimulated-gene-expression-in-microglia
#4
Ashley McDonough, Richard V Lee, Shahani Noor, Chungeun Lee, Thu Le, Michael Iorga, Jessica L H Phillips, Sean Murphy, Thomas Möller, Jonathan R Weinstein
Innate immune signaling is important in the pathophysiology of ischemia/reperfusion (stroke) induced injury and recovery. Several lines of evidence support a central role for microglia in these processes. Recent work has identified Toll-like receptors (TLRs) and type I interferon (IFN) signaling in both ischemia/reperfusion-induced brain injury and ischemic preconditioning-mediated neuroprotection. To determine the effects of 'ischemia/reperfusion-like' conditions on microglia we carried out genomic analyses on wild-type (WT) and TLR4(-/-) cultured microglia following sequential exposure to hypoxia/hypoglycemia and normoxia/normoglycemia (H/H-N/N)...
July 26, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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
#5
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/28745271/nuclear-domain-10-components-upregulated-via-interferon-during-human-cytomegalovirus-infection-potently-regulate-viral-infection
#6
Caroline L Ashley, Mandy S Glass, Allison Abendroth, Brian P McSharry, Barry Slobedman
Human cytomegalovirus (HCMV) is a ubiquitous betaherpesvirus that causes life-threatening disease in immunocompromised and immunonaïve individuals. Type I interferons (IFNs) are crucial molecules in the innate immune response to HCMV and are also known to upregulate several components of the interchromosomal multiprotein aggregates collectively referred to as nuclear domain 10 (ND10). In the context of herpesvirus infection, ND10 components are known to restrict gene expression. This raises the question as to whether key ND10 components (PML, Sp100 and hDaxx) act as anti-viral IFN-stimulated genes (ISGs) during HCMV infection...
July 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28744851/post-translational-regulation-of-antiviral-innate-signaling
#7
REVIEW
Yilong Zhou, Chenxi He, Wang Lin, Baoxue Ge
The innate immune system initiates immune responses by pattern-recognition receptors (PRR). Virus-derived nucleic acids are sensed by the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family and the toll-like receptor (TLR) family as well as the DNA sensor cyclic GMP-AMP (cGAMP) synthase (cGAS). These receptors activate IRF3/7 and NF-κB signaling pathways to induce the expression of type I interferons (IFNs) and other cytokines firing antiviral responses within the cell. However, to achieve a favorable outcome for the host, a balanced production of IFNs and activation of antiviral responses is required...
July 26, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28743914/cyclic-gmp-amp-ameliorates-diet-induced-metabolic-dysregulation-and-regulates-proinflammatory-responses-distinctly-from-sting-activation
#8
Xin Guo, Chang Shu, Honggui Li, Ya Pei, Shih-Lung Woo, Juan Zheng, Mengyang Liu, Hang Xu, Rachel Botchlett, Ting Guo, Yuli Cai, Xinsheng Gao, Jing Zhou, Lu Chen, Qifu Li, Xiaoqiu Xiao, Linglin Xie, Ke K Zhang, Jun-Yuan Ji, Yuqing Huo, Fanyin Meng, Gianfranco Alpini, Pingwei Li, Chaodong Wu
Endogenous cyclic GMP-AMP (cGAMP) binds and activates STING to induce type I interferons. However, whether cGAMP plays any roles in regulating metabolic homeostasis remains unknown. Here we show that exogenous cGAMP ameliorates obesity-associated metabolic dysregulation and uniquely alters proinflammatory responses. In obese mice, treatment with cGAMP significantly decreases diet-induced proinflammatory responses in liver and adipose tissues and ameliorates metabolic dysregulation. Strikingly, cGAMP exerts cell-type-specific anti-inflammatory effects on macrophages, hepatocytes, and adipocytes, which is distinct from the effect of STING activation by DMXAA on enhancing proinflammatory responses...
July 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28742068/a-peptide-based-viral-inactivator-inhibits-zika-virus-infection-in-pregnant-mice-and-fetuses
#9
Yufeng Yu, Yong-Qiang Deng, Peng Zou, Qian Wang, Yanyan Dai, Fei Yu, Lanying Du, Na-Na Zhang, Min Tian, Jia-Nan Hao, Yu Meng, Yuan Li, Xiaohui Zhou, Jasper Fuk-Woo Chan, Kwok-Yung Yuen, Cheng-Feng Qin, Shibo Jiang, Lu Lu
Zika virus (ZIKV), a re-emerging flavivirus associated with neurological disorders, has spread rapidly to more than 70 countries and territories. However, no specific vaccines or antiviral drugs are currently available to prevent or treat ZIKV infection. Here we report that a synthetic peptide derived from the stem region of ZIKV envelope protein, designated Z2, potently inhibits infection of ZIKV and other flaviviruses in vitro. We show that Z2 interacts with ZIKV surface protein and disrupts the integrity of the viral membrane...
July 25, 2017: Nature Communications
https://www.readbyqxmd.com/read/28738907/rig-i-expression-in-perifascicular-myofibers-is-a-reliable-biomarker-of-dermatomyositis
#10
Xavier Suárez-Calvet, Eduard Gallardo, Iago Pinal-Fernandez, Noemi De Luna, Cinta Lleixà, Jordi Díaz-Manera, Ricardo Rojas-García, Ivan Castellví, M Angeles Martínez, Josep M Grau, Albert Selva-O'Callaghan, Isabel Illa
BACKGROUND: Dermatomyositis (DM) is inflammatory myopathy or myositis characterized by muscle weakness and skin manifestations. In the differential diagnosis of DM the evaluation of the muscle biopsy is of importance among other parameters. Perifascicular atrophy in the muscle biopsy is considered a hallmark of DM. However, perifascicular atrophy is not observed in all patients with DM and, conversely, perifascicular atrophy can be observed in other myositis such as antisynthetase syndrome (ASS), complicating DM diagnosis...
July 24, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28738877/unexpected-complexity-in-the-interference-activity-of-a-cloned-influenza-defective-interfering-rna
#11
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/28738021/commensal-bacteria-ab-use-cd8-t-cells-to-induce-insulin-resistance
#12
REVIEW
Chi Ma, Tim F Greten
Type I interferon-dependent expansion of intrahepatic CD8(+) T cells promotes systemic insulin resistance in obesity.
April 21, 2017: Science Immunology
https://www.readbyqxmd.com/read/28738017/distinct-oxysterol-requirements-for-positioning-na%C3%A3-ve-and-activated-dendritic-cells-in-the-spleen
#13
Erick Lu, Eric V Dang, Jeffrey G McDonald, Jason G Cyster
Correct positioning of dendritic cells (DCs) is critical for efficient pathogen encounter and antigen presentation. Epstein-Barr virus-induced gene 2 (EBI2) has been identified as a chemoattractant receptor required for naïve CD4(+)DCIR2(+) DC positioning in response to 7α,25-hydroxycholesterol (7α,25-HC). We now provide evidence that a second EBI2 ligand, 7α,27-HC, is involved in splenic DCIR2(+) DC positioning and homeostasis. Cyp27a1, the enzyme uniquely required for 7α,27-HC synthesis, is expressed by stromal cells in the region of naïve DC localization...
April 7, 2017: Science Immunology
https://www.readbyqxmd.com/read/28736973/plasmacytoid-dendritic-cells-and-type-i-interferon-in-the-immunological-response-against-warts
#14
D Saadeh, M Kurban, O Abbas
BACKGROUND: Plasmacytoid dendritic cells (pDCs) are the most potent producers of type I interferons (IFNs), and are involved in the pathogenesis of several cutaneous infectious (especially viral), inflammatory/autoimmune and neoplastic entities. Their role in the pathogenesis and regression of human papilloma virus (HPV)-induced skin lesions has not been well studied. AIM: To investigate pDC occurrence and activity in HPV-induced skin lesions, including inflamed and uninflamed warts as well as epidermodysplasia verruciformis (EDV)-associated lesions...
July 24, 2017: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/28736121/potential-of-circulatory-procalcitonin-as-a-biomarker-reflecting-inflammation-among-south-indian-diabetic-foot-ulcers
#15
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/28734654/schlafen-14-slfn14-is-a-novel-antiviral-factor-involved-in-the-control-of-viral-replication
#16
Rak-Kyun Seong, Seong-Wook Seo, Ji-Ae Kim, Sarah J Fletcher, Neil V Morgan, Mukesh Kumar, Young-Ki Choi, Ok Sarah Shin
Schlafen (SLFN) proteins have been suggested to play important functions in cell proliferation and immune cell development. In this study, we determined the antiviral activities of putative RNA-helicase domain-containing SLFN14. Murine SLFN14 expression was specifically induced by TLR3-mediated pathways and type I interferon (IFN) in RAW264.7 mouse macrophages. To examine the role of SLFN during viral infection, cells were infected with either wild-type PR8 or delNS1/PR8 virus. SLFN14 expression was specifically induced following influenza virus infection...
July 11, 2017: Immunobiology
https://www.readbyqxmd.com/read/28733313/granzyme-a-deficiency-breaks-immune-tolerance-and-promotes-autoimmune-diabetes-through-a-type-i-interferon-dependent-pathway
#17
Zia Ua Mollah, Hong Sheng Quah, Kate L Graham, Gaurang Jhala, Balasubramanian Krishnamurthy, Joanna Francisca M Dharma, Jonathan Chee, Prerak M Trivedi, Evan G Pappas, Leanne Mackin, Edward Pf Chu, Satoru Akazawa, Stacey Fynch, Charlotte Hodson, Andrew J Deans, Joseph A Trapani, Mark Mw Chong, Phillip I Bird, Thomas C Brodnicki, Helen E Thomas, Thomas Wh Kay
Granzyme A is a protease implicated in the degradation of intracellular DNA. Nucleotide complexes are known triggers of systemic autoimmunity, but a role in organ-specific autoimmune disease has not been demonstrated. To investigate whether such a mechanism could be an endogenous trigger for autoimmunity, we examined the impact of granzyme A deficiency in the NOD mouse model of autoimmune diabetes. Granzyme A deficiency resulted in an increased incidence in diabetes associated with accumulation of single stranded DNA in immune cells and induction of an interferon response in pancreatic islets...
July 21, 2017: Diabetes
https://www.readbyqxmd.com/read/28732227/atm-supports-gammaherpesvirus-replication-by-attenuating-type-i-interferon-pathway
#18
Eric J Darrah, Kyle P Stoltz, Mitchell Ledwith, Vera L Tarakanova
Ataxia-Telangiectasia mutated (ATM) kinase participates in multiple networks, including DNA damage response, oxidative stress, and mitophagy. ATM also supports replication of diverse DNA and RNA viruses. Gammaherpesviruses are prevalent cancer-associated viruses that benefit from ATM expression during replication. This proviral role of ATM had been ascribed to its signaling within the DNA damage response network; other functions of ATM have not been considered. In this study increased type I interferon (IFN) responses were observed in ATM deficient gammaherpesvirus-infected macrophages...
July 18, 2017: Virology
https://www.readbyqxmd.com/read/28729212/the-influence-of-temperature-on-viral-replication-and-antiviral-related-genes-response-in-hirame-rhabdovirus-infected-flounder-paralichthys-olivaceus
#19
Jialin Zhang, Xiaoqian Tang, Xiuzhen Sheng, Jing Xing, Wenbin Zhan
Hirame rhabdovirus (HIRRV) is a rhabdovirus that causes severe disease in fish. The mortality due to HIRRV infection occurs at temperatures below 15 °C, but no mortality is observed over 20 °C. In this study, Japanese flounder (Paralichthys olivaceus) was artificially infected with the HIRRV CNPo2015 strain at 10 °C or 20 °C. Absolute quantitative real-time PCR was employed to examine the viral replication in spleens after HIRRV infection. Expression profiles of four interferon-related genes (type I IFN, Mx, ISG15, MDA5) and two proinflammatory genes (TNF-α and IL-1β) were also investigated by quantitative real-time PCR...
July 17, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28728846/the-effects-of-type-i-interferon-on-glioblastoma-cancer-stem-cells
#20
Ziyun Du, Chun Cai, Michelle Sims, Frederick A Boop, Andrew M Davidoff, Lawrence M Pfeffer
Glioblastomas (GBMs) are highly invasive brain tumors that are extremely deadly. The highly aggressive nature of GBM as well as its heterogeneity at the molecular and cellular levels has been attributed to a rare subpopulation of GBM stem-like cells (GSCs). Interferons (IFNs) are a family of endogenous antiviral proteins that have anticancer activity in vitro, and have been used clinically to treat GBM. IFN inhibits the proliferation of various established GBM cell lines, but the effects of IFNs on GSCs remain relatively unknown...
July 17, 2017: Biochemical and Biophysical Research Communications
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