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type 1 interferon

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https://www.readbyqxmd.com/read/28238527/interferon-alpha-impairs-insulin-production-in-human-beta-cells-via-endoplasmic-reticulum-stress
#1
Angela Lombardi, Yaron Tomer
Despite substantial advances in the research exploring the pathogenesis of Type 1 Diabetes (T1D), the pathophysiological mechanisms involved remain unknown. We hypothesized in this study that interferon alpha (IFNα) participates in the early stages of T1D development by triggering endoplasmic reticulum (ER) stress. To verify our hypothesis, human islets and human EndoC-βH1 cells were exposed to IFNα and tested for ER stress markers, glucose stimulated insulin secretion (GSIS) and insulin content. IFNα treatment induced upregulation of ER stress markers including Binding immunoglobulin Protein, phospho-eukaryotic translation initiation factor 2α, spliced- X-box binding protein-1, C/EBP homologous protein and activating transcription factor 4...
February 23, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28236279/oas-gene-family-expression-is-associated-with-hiv-related-neurocognitive-disorders
#2
C Sanfilippo, M R Pinzone, D Cambria, A Longo, M Palumbo, R Di Marco, F Condorelli, G Nunnari, L Malaguarnera, M Di Rosa
HIV-associated neurocognitive disorders are common in HIV-infected individuals, even in the combination antiretroviral therapy (c-ART) era. Several mechanisms are involved in neuronal damage, including chronic inflammation immune activation. Mammalian 2'-5'-oligoadenylate synthetase (OAS) genes are produced in response to interferon (IFN), mainly by monocytes, and exert their antiviral functions by activation of RNase L that degrades viral and cellular RNAs. In this study, we aimed at exploring OAS gene family RNA expression in simian immunodeficiency virus encephalitis (SIVE), in HIV-associated neurocognitive disorders (HAND), and in HIV-associate dementia (HAD)...
February 24, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28230086/classification-of-idiopathic-interstitial-pneumonias-using-anti-myxovirus-resistance-protein-1-autoantibody
#3
Yoshimasa Hamano, Hiroshi Kida, Shoichi Ihara, Akihiro Murakami, Masahiro Yanagawa, Ken Ueda, Osamu Honda, Lokesh P Tripathi, Toru Arai, Masaki Hirose, Toshimitsu Hamasaki, Yukihiro Yano, Tetsuya Kimura, Yasuhiro Kato, Hyota Takamatsu, Tomoyuki Otsuka, Toshiyuki Minami, Haruhiko Hirata, Koji Inoue, Izumi Nagatomo, Yoshito Takeda, Masahide Mori, Hiroyoshi Nishikawa, Kenji Mizuguchi, Takashi Kijima, Masanori Kitaichi, Noriyuki Tomiyama, Yoshikazu Inoue, Atsushi Kumanogoh
Chronic fibrosing idiopathic interstitial pneumonia (IIP) can be divided into two main types: idiopathic pulmonary fibrosis (IPF), a steroid-resistant and progressive disease with a median survival of 2-3 years, and idiopathic non-specific interstitial pneumonia (INSIP), a steroid-sensitive and non-progressive autoimmune disease. Although the clinical courses of these two diseases differ, they may be difficult to distinguish at diagnosis. We performed a comprehensive analysis of serum autoantibodies from patients definitively diagnosed with IPF, INSIP, autoimmune pulmonary alveolar proteinosis, and sarcoidosis...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28229507/a-samhd1-mutation-associated-with-aicardi-gouti%C3%A3-res-syndrome-uncouples-the-ability-of-samhd1-to-restrict-hiv-1-from-its-ability-to-downmodulate-type-i-interferon-in-humans
#4
Tommy E White, Alberto Brandariz-Nuñez, Alicia Martinez-Lopez, Caitlin Knowlton, Gina Lenzi, Baek Kim, Dmitri Ivanov, Felipe Diaz-Griffero
Mutations in the human SAMHD1 gene are known to correlate with the development of the Aicardi-Goutières Syndrome (AGS), which is an inflammatory encephalopathy that exhibits neurological dysfunction characterized by increased production of type I interferon (IFN); this evidence has lead to the concept that the SAMHD1 protein negatively regulates the type I IFN response. Additionally, the SAMHD1 protein has been shown to prevent efficient HIV-1 infection of macrophages, dendritic cells and resting CD4+ T cells...
February 22, 2017: Human Mutation
https://www.readbyqxmd.com/read/28223351/in-vivo-and-in-vitro-proteome-analysis-of-hiv-1-infected-human-cd4-t-cells
#5
Johannes Nemeth, Valentina Vongrad, Karin J Metzner, Victoria Strouvelle, Rainer Weber, Patrick Pedrioli, Ruedi Aebersold, Huldrych Guenthard, Ben C Collins
Host directed therapies against HIV-1 are thought to be critical for long term containment of the HIV-1 pandemic but remain elusive. Since HIV-1 infects and manipulates important effectors of both the innate and adaptive immune system, identifying modulations of the host cell systems in humans during HIV-1 infection may be crucial for the development of immune based therapies. Here, we quantified the changes of the proteome in human CD4+ T cells upon HIV-1 infection, both in vitro and in vivo. A SWATH-MS approach was used to measure the proteome of human primary CD4+ T cells infected with HIV-1 in vitro as well as CD4+ T cells from HIV-1 infected patients with paired samples on and off antiretroviral treatment...
February 21, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28223169/igf1-igf1r-stat3-signaling-inducible-ifitm2-promotes-gastric-cancer-growth-and-metastasis
#6
Li Xu, Rui Zhou, Lezhong Yuan, Shiqing Wang, Xiaoyin Li, Huanrong Ma, Minyu Zhou, Changqie Pan, Jingwen Zhang, Na Huang, Min Shi, Jianping Bin, Yulin Liao, Wangjun Liao
Interferon-induced transmembrane proteins (IFITMs) are expressed in some types of cancer. However, their precise roles in tumor progression remain unclear. The present study investigated the function of IFITM2 in gastric cancer (GC) progression. A retrospective analysis of a public database and 167 GC patients revealed that IFITM2 expression was upregulated in gastric tumor samples, which was positively correlated with disease progression, more frequent postoperative recurrence, and higher mortality rate. IFITM2 knockdown decreased GC cell proliferation, migration, invasion, and epithelial-to-mesenchymal transition in vitro...
February 20, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28222752/dendritic-cells-macrophages-nk-and-cd8-t-lymphocytes-play-pivotal-roles-in-controlling-hsv-1-in-the-trigeminal-ganglia-by-producing-il1-beta-inos-and-granzyme-b
#7
Natália Lucinda, Maria Marta Figueiredo, Natália Lima Pessoa, Beatriz Senra Álvares da Silva Santos, Graciela Kunrath Lima, Arthur Molinari Freitas, Alexandre Magalhães Vieira Machado, Erna Geessien Kroon, Lis Ribeiro do Valle Antonelli, Marco Antônio Campos
BACKGROUND: Herpes simplex virus type 1 (HSV-1) cause not only mild symptoms but also blindness and encephalitis. It was previously shown that the immune response against HSV-1 occurs mainly in the trigeminal ganglia (TG) and that Toll-like receptors 2 and 9 (TLR2/9) are important in mediating this response. It was also demonstrated that iNOS (nitric oxide synthase) and interleukin 1 beta (IL-1β) play an essential role in the defense against HSV-1 infection. Importantly, the present work aimed to identify the primary cells responsible for iNOS and IL-1β production and search for other important molecules and cells that might or might not depend on TLR2/9 receptors to mediate the immune response against HSV-1...
February 21, 2017: Virology Journal
https://www.readbyqxmd.com/read/28222218/reduced-inflammatory-responses-of-follicular-helper-t-cell-promote-the-development-of-regulatory-b-cells-after-roux-en-y-gastric-bypass
#8
Junfang Zhan, Liyu Huang, Haiyong Ma, Huan Chen, Yuan Yang, Sheng Tan, Wendy Song, Weiguo Zhao, Xiaojiang Dai
Bariatric surgery is currently the most effective strategy in treating severe obesity and its comorbidities, such as type 2 diabetes (T2D). However, the mechanism through which bariatric surgery mediates its benefits is not completely understood. Since obesity and T2D represent yet another inflammatory disease, and follicular helper T (Tfh) cells play important roles in inflammatory disorders, we investigated whether the Tfh activity was altered after Roux-en-Y gastric bypass (RYGB), one of the most common bariatric surgery procedures...
February 21, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28219017/interaction-between-fmdv-l-pro-and-transcription-factor-adnp-is-required-for-optimal-viral-replication
#9
Gisselle N Medina, Giselle M Knudsen, Alexander L Greninger, Anna Kloc, Fayna Díaz-San Segundo, Elizabeth Rieder, Marvin J Grubman, Joseph L DeRisi, Teresa de Los Santos
The foot-and-mouth disease virus (FMDV) leader protease (L(pro)) inhibits host translation and transcription affecting the expression of several factors involved in innate immunity. In this study, we have identified the host transcription factor ADNP (activity dependent neuroprotective protein) as an L(pro) interacting protein by mass spectrometry. We show that L(pro) can bind to ADNP in vitro and in cell culture. RNAi of ADNP negatively affected virus replication and higher levels of interferon (IFN) and IFN-stimulated gene expression were detected...
February 17, 2017: Virology
https://www.readbyqxmd.com/read/28216632/resveratrol-treatment-reveals-a-novel-role-for-hmgb1-in-regulation-of-the-type-1-interferon-response-in-dengue-virus-infection
#10
Nurhafiza Zainal, Chih-Peng Chang, Yi-Lin Cheng, Yan-Wei Wu, Robert Anderson, Shu-Wen Wan, Chia-Ling Chen, Tzong-Shiann Ho, Sazaly AbuBakar, Yee-Shin Lin
Dengue is one of the most significant mosquito-borne virus diseases worldwide, particularly in tropical and subtropical regions. This study sought to examine the antiviral activity of resveratrol (RESV), a phytoalexin secreted naturally by plants, against dengue virus (DENV) infection. Our data showed that RESV inhibits the translocation of high mobility group box 1 (HMGB1), a DNA binding protein that normally resides in the nucleus, into the cytoplasm and extracellular milieu. HMGB1 migrates out of the nucleus during DENV infection...
February 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28215221/targeting-chromatin-remodeling-in-inflammation-and-fibrosis
#11
J Yang, B Tian, A R Brasier
Mucosal surfaces of the human body are lined by a contiguous epithelial cell surface that forms a barrier to aerosolized pathogens. Specialized pattern recognition receptors detect the presence of viral pathogens and initiate protective host responses by triggering activation of the nuclear factor κB (NFκB)/RelA transcription factor and formation of a complex with the positive transcription elongation factor (P-TEFb)/cyclin-dependent kinase (CDK)9 and Bromodomain-containing protein 4 (BRD4) epigenetic reader...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28214358/the-n-terminus-of-cgas-de-oligomerizes-the-cgas-dna-complex-and-lifts-the-dna-size-restriction-of-core-cgas-activity
#12
Arum Lee, Eun-Byeol Park, Janghyun Lee, Byong-Seok Choi, Suk-Jo Kang
Cyclic GMP-AMP synthase (cGAS) is a DNA-sensing enzyme in the innate immune system. Recent studies using core-cGAS lacking the N-terminus investigated the mechanism for binding of double-stranded (ds) DNA and synthesis of 2',3'-cGAMP, a secondary messenger that ultimately induces type I interferons. However, the function of the N-terminus of cGAS remains largely unknown. Here, we found that the N-terminus enhanced the activity of core-cGAS in vivo. Importantly, the catalytic activity of core-cGAS decreased as the length of dsDNA increased, but the diminished activity was restored by addition of the N-terminus...
February 18, 2017: FEBS Letters
https://www.readbyqxmd.com/read/28213522/type-i-interferon-regulated-gene-expression-and-signaling-in-murine-mixed-glial-cells-lacking-signal-transducers-and-activators-of-transcription-1-or-2-or-interferon-regulatory-factor-9
#13
Wen Li, Markus J Hofer, Pattama Songkhunawej, So Ri Jung, Dale Hancock, Gareth Denyer, Iain L Campbell
Type I interferons (IFN-I) are critical in antimicrobial and antitumor defense. Although IFN-I signal via the interferon-stimulated gene factor 3 (ISGF3) complex consisting of STAT1, STAT2 and IRF9, IFN-I can mediate significant biological effects via ISGF3-independent pathways. For example, absence of STAT1, STAT2 or IRF9 exacerbates neurological disease in transgenic mice with CNS-production of IFN-Ι. Here we determined the role of IFN-I-driven, ISGF3-independent signaling in regulating global gene expression in STAT1, STAT2 or IRF9-deficient murine mixed glial cell cultures (MGCs)...
February 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28211040/anti-cd3-treatment-upregulates-pd-1-expression-on-activated-effector-t-cells-and-severely-impairs-their-inflammatory-capacity
#14
Maja Wallberg, Asha Recino, Jenny Phillips, Duncan Howie, Margaux Vienne, Christopher Paluch, Miyuki Azuma, F Susan Wong, Herman Waldmann, Anne Cooke
T cells play a key role in the pathogenesis of type 1 diabetes, and targeting the CD3 component of the TCR complex provides one therapeutic approach. Anti-CD3 treatment can reverse overt disease in spontaneously diabetic non-obese diabetic mice, an effect proposed to, at least in part, be caused by a selective depletion of pathogenic cells. We have used a transfer model to further investigate the effects of anti-CD3 treatment on green fluorescent protein (GFP)(+) islet-specific effector T cells in vivo. The GFP expression allowed us to isolate the known effectors at different time points during treatment to assess cell presence in various organs as well as gene expression and cytokine production...
February 17, 2017: Immunology
https://www.readbyqxmd.com/read/28205069/transcriptomic-analysis-of-thp-1-macrophages-exposed-to-lipoprotein-hydrolysis-products-generated-by-lipoprotein-lipase
#15
Narmadaa Thyagarajan, Jenika D Marshall, Arthur T Pickett, Clemens Schumacher, Yanbo Yang, Sherri L Christian, Robert J Brown
Macrophage lipoprotein lipase (LPL) induces lipid accumulation and promotes atherosclerosis. However, the effects of lipoprotein hydrolysis products generated by LPL on macrophage-derived foam cell formation are not clearly understood. Thus, we analyzed the transcriptomic response to hydrolysis products via microarray analyses on RNA isolated from human THP-1 macrophages incubated with total lipoprotein hydrolysis products generated by LPL. The expression of 183 transcripts was significantly upregulated and 133 transcripts were significantly downregulated...
March 2017: Lipids
https://www.readbyqxmd.com/read/28202040/subcellular-localization-and-interactions-of-infectious-salmon-anemia-virus-isav-m1-and-nep-as-well-as-host-hsc70
#16
Wenting Zhang, Chengzhi Cai, Li Lin, Yizhi Jane Tao, Meilin Jin
BACKGROUND: Infectious salmon anemia virus (ISAV) is an important fish pathogen that causes high mortality in farmed Atlantic salmon. The ISAV genome consists of eight single-stranded, negative-sense RNA segments. The six largest segments contain one open reading frame (ORF) each, and encode three polymerase proteins, nucleoprotein, fusion protein, and hemagglutinin esterase protein. The two smallest segments contain more than one ORF each. The segment 7 encodes non-structural protein 1 (NS1) and nuclear export protein (NEP), while segment 8 encodes matrix protein 1 and 2 (M1 and M2)...
February 15, 2017: Virology Journal
https://www.readbyqxmd.com/read/28199372/endometrial-factors-similarly-induced-by-ifnt2-and-ifntc1-through-transcription-factor-foxs1
#17
Kazuya Kusama, Rulan Bai, Keigo Nakamura, Sayaka Okada, Jiro Yasuda, Kazuhiko Imakawa
In ruminants, Interferon tau (IFNT) is the pregnancy recognition protein produced by the mononuclear trophectoderm of the conceptus, and is secreted into the uterine lumen during the peri-attachment period. In our previous study, the high-throughput RNA sequencing (RNA-seq) data obtained from bovine conceptuses during the peri-attachment period identified two IFNT mRNAs, IFNT2 and IFNTc1. However, how each of these IFNT variants regulates endometrial gene expression has not been characterized. Using RNA-seq analysis, we evaluated how IFNT2 and IFNTc1 affected transcript expression in primary bovine endometrial epithelial cells (EECs)...
2017: PloS One
https://www.readbyqxmd.com/read/28196914/the-host-microrna-mir-301a-blocks-the-irf1-mediated-neuronal-innate-immune-response-to-japanese-encephalitis-virus-infection
#18
Bibhabasu Hazra, Kanhaiya Lal Kumawat, Anirban Basu
Effective recognition of viral components and the subsequent stimulation of the production of type I interferons (IFNs) is crucial for the induction of host antiviral immunity. The failure of the host to efficiently produce type I IFNs in response to infection by the Japanese encephalitis virus (JEV) is linked with an increased probability for the disease to become lethal. JEV is a neurotropic virus of the Flaviviridae family that causes encephalitis in humans. JEV infection is regulated by several host factors, including microRNAs, which are conserved noncoding RNAs that participate in various physiological and pathological processes...
February 14, 2017: Science Signaling
https://www.readbyqxmd.com/read/28196594/inactivation-of-interferon-receptor-promotes-the-establishment-of-immune-privileged-tumor-microenvironment
#19
Kanstantsin V Katlinski, Jun Gui, Yuliya V Katlinskaya, Angelíca Ortiz, Riddhita Chakraborty, Sabyasachi Bhattacharya, Christopher J Carbone, Daniel P Beiting, Melanie A Girondo, Amy R Peck, Ellen Puré, Priya Chatterji, Anil K Rustgi, J Alan Diehl, Constantinos Koumenis, Hallgeir Rui, Serge Y Fuchs
Refractoriness of solid tumors, including colorectal cancers (CRCs), to immunotherapies is attributed to the immunosuppressive tumor microenvironment that protects malignant cells from cytotoxic T lymphocytes (CTLs). We found that downregulation of the type I interferon receptor chain IFNAR1 occurs in human CRC and mouse models of CRC. Downregulation of IFNAR1 in tumor stroma stimulated CRC development and growth, played a key role in formation of the immune-privileged niche, and predicted poor prognosis in human CRC patients...
February 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28193529/heterogeneity-in-immune-marker-expression-after-acquisition-of-resistance-to-egfr-kinase-inhibitors-analysis-of-a-case-with-small-cell-lung-cancer-transformation
#20
Kenichi Suda, Isao Murakami, Hui Yu, Jihye Kim, Kim Ellison, Christopher J Rivard, Tetsuya Mitsudomi, Fred R Hirsch
INTRODUCTION: Expression of immune-markers is of scientific interest due to their potential roles as predictive biomarkers for immunotherapy. Although the microenvironment of metastatic tumors and/or therapy-inducible histological transformation may affect the expression of these immune-markers, there is little data regarding this context. METHODS: A 76-year-old never-smoking female with epidermal growth factor receptor (EGFR) mutated lung adenocarcinoma (AC) acquired resistance to gefitinib...
February 10, 2017: Journal of Thoracic Oncology
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