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https://www.readbyqxmd.com/read/29661858/rna-sensor-lgp2-inhibits-traf-ubiquitin-ligase-to-negatively-regulate-innate-immune-signaling
#1
Jean-Patrick Parisien, Jessica J Lenoir, Roli Mandhana, Kenny R Rodriguez, Kenin Qian, Annie M Bruns, Curt M Horvath
The production of type I interferon (IFN) is essential for cellular barrier functions and innate and adaptive antiviral immunity. In response to virus infections, RNA receptors RIG-I and MDA5 stimulate a mitochondria-localized signaling apparatus that uses TRAF family ubiquitin ligase proteins to activate master transcription regulators IRF3 and NFκB, driving IFN and antiviral target gene expression. Data indicate that a third RNA receptor, LGP2, acts as a negative regulator of antiviral signaling by interfering with TRAF family proteins...
April 16, 2018: EMBO Reports
https://www.readbyqxmd.com/read/29657141/association-of-serum-soluble-cd163-with-polymyositis-and-dermatomyositis-especially-in-anti-mda5-antibody-positive-cases
#2
Hidenaga Kawasumi, Yasuhiro Katsumata, Akira Nishino, Shinya Hirahara, Yasushi Kawaguchi, Masataka Kuwana, Hisashi Yamanaka
OBJECTIVE: We elucidated the association of serum soluble CD163 (sCD163) with rapidly progressive interstitial lung disease (RP-ILD), autoantibody profiles, and serum ferritin in patients with polymyositis (PM), classic dermatomyositis (DM), and clinical amyopathic dermatomyositis (CADM). METHODS: Serum sCD163 levels were retrospectively measured by ELISA in patients with PM, classic DM, and CADM, as well as in healthy controls (HC). Repeat sera samples were obtained posttreatment from available patients...
April 15, 2018: Journal of Rheumatology
https://www.readbyqxmd.com/read/29600494/duox2-induced-innate-immune-responses-in-the-respiratory-epithelium-and-intranasal-delivery-of-duox2-dna-using-polymer-that-mediates-immunization
#3
REVIEW
Yung Jin Jeon, Hyun Jik Kim
Respiratory mucosa especially nasal epithelium is well known as the first-line barrier of air-borne pathogens. High levels of reactive oxygen species (ROS) are detected in in vitro cultured human epithelial cells and in vivo lung. With identification of NADPH oxidase (Nox) system of respiratory epithelium, the antimicrobial role of ROS has been studied. Duox2 is the most abundant Nox isoform and produces the regulated amount of ROS in respiratory epithelium. Duox2-derived ROS are involved in antiviral innate immune responses but more studies are needed to verify the mechanism...
March 30, 2018: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29599452/direct-antiviral-properties-of-tlr-ligands-against-hbv-replication-in-immune-competent-hepatocytes
#4
Julie Lucifora, Marc Bonnin, Ludovic Aillot, Floriane Fusil, Sarah Maadadi, Laura Dimier, Maud Michelet, Océane Floriot, Anaïs Ollivier, Michel Rivoire, Malika Ait-Goughoulte, Stéphane Daffis, Simon P Fletcher, Anna Salvetti, François-Loïc Cosset, Fabien Zoulim, David Durantel
Current therapies for chronic hepatitis B virus (HBV) infections are effective at decreasing the viral load in serum, but do not lead to viral eradication. Recent studies highlighted the therapeutic or "adjuvant" potential of immune-modulators. Our aim was to explore the direct anti-HBV effect of Toll-Like-Receptors (TLR) agonists in hepatocytes. HBV-infected primary human hepatocytes (PHH) or differentiated HepaRG cells (dHepaRG) were treated with various TLR agonists. Amongst all TLR ligands tested, Pam3CSK4 (TLR1/2-ligand) and poly(I:C)-(HMW) (TLR3/MDA5-ligand) were the best at reducing all HBV parameters...
March 29, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29592874/decreased-a-to-i-rna-editing-as-a-source-of-keratinocytes-dsrna-in-psoriasis
#5
Lea Shallev, Eli Kopel, Ariel Feiglin, Gil S Leichner, Dror Avni, Yehezkel Sidi, Eli Eisenberg, Aviv Barzilai, Erez Y Levanon, Shoshana Greenberger
Recognition of dsRNA molecules activates the MDA5-MAVS pathway, and plays a critical role in stimulating type-I interferon responses in psoriasis. However, the source of the dsRNA accumulation in psoriatic keratinocytes remains largely unknown. A-to-I RNA editing is a common co- or post-transcriptional modification that diversifies adenosine in dsRNA, and leads to unwinding of dsRNA structures. Thus, impaired RNA editing activity can result in an increased load of endogenous dsRNAs. Here we provide a transcriptome wide analysis of RNA editing across dozens of psoriasis patients, and demonstrate a global editing reduction in psoriatic lesions...
March 28, 2018: RNA
https://www.readbyqxmd.com/read/29581525/innate-immune-system-activation-in-zebrafish-and-cellular-models-of-diamond-blackfan-anemia
#6
Nadia Danilova, Mark Wilkes, Elena Bibikova, Min-Young Youn, Kathleen M Sakamoto, Shuo Lin
Deficiency of ribosomal proteins (RPs) leads to Diamond Blackfan Anemia (DBA) associated with anemia, congenital defects, and cancer. While p53 activation is responsible for many features of DBA, the role of immune system is less defined. The Innate immune system can be activated by endogenous nucleic acids from non-processed pre-rRNAs, DNA damage, and apoptosis that occurs in DBA. Recognition by toll like receptors (TLRs) and Mda5-like sensors induces interferons (IFNs) and inflammation. Dying cells can also activate complement system...
March 26, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29579373/calcinosis-of-the-mandible-in-dermatomyositis
#7
Andrea Fava, Lisa Christopher-Stine
A 52-year-old woman presented to the Rheumatology clinic complaining of new tender nodules along the inferior border of her jaw. She has an 8-year history of amyopathic dermatomyositis with anti-MDA5 antibodies complicated by interstitial lung disease. Her current treatments include tacrolimus, prednisone and hydroxychloroquine. She noticed the nodules during the most recent flare of her skin disease one month prior. On exam, she had 2 tender, hard, mobile nodules measuring approximately 5mm each located at 4cm and 2...
March 26, 2018: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29572905/infection-with-a-brazilian-isolate-of-zika-virus-generates-rig-i-stimulatory-rna-and-the-viral-ns5-protein-blocks-type-i-ifn-induction-and-signalling
#8
Jonny Hertzog, Antonio Gregorio Dias Junior, Rachel E Rigby, Claire L Donald, Alice Mayer, Erdinc Sezgin, Chaojun Song, Boquan Jin, Philip Hublitz, Christian Eggeling, Alain Kohl, Jan Rehwinkel
Zika virus (ZIKV) is a major public health concern in the Americas. We report that ZIKV infection and RNA extracted from ZIKV infected cells potently activated the induction of type I interferons (IFNs). This effect was fully dependent on the mitochondrial antiviral signalling protein (MAVS), implicating RIG-I-like receptors (RLRs) as upstream sensors of viral RNA. Indeed, RIG-I and the related RNA sensor MDA5 contributed to type I IFN induction in response to RNA from infected cells. We found that ZIKV NS5 from a recent Brazilian isolate blocked type I IFN induction downstream of RLRs and also inhibited type I IFN receptor (IFNAR) signalling...
March 23, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29567028/analysis-of-host-toll-like-receptor-3-and-rig-i-like-receptor-gene-expression-in-patients-with-abdominal-aortic-aneurysm
#9
Agnieszka Jabłońska, Christoph Neumayer, Michael Bolliger, Bernd Gollackner, Markus Klinger, Edyta Paradowska, Josif Nanobachvili, Ihor Huk
OBJECTIVE: Abdominal aortic aneurysm (AAA) is a vascular disease relatively common in the elderly population. Although some events that contribute to the development and progression of AAA are known, there are limited data examining the association of Toll-like receptor 3 (TLR3) and RIG-I-like receptor expression with the pathogenesis of AAAs. In this study, we investigated the gene and protein expression of TLR3 and RIG-I-like receptors (RIG-I and MDA5) in aortic wall and blood of AAA patients and examined the relationship between their expression and immune response...
March 19, 2018: Journal of Vascular Surgery
https://www.readbyqxmd.com/read/29559532/innate-responses-to-gene-knockouts-impact-overlapping-gene-networks-and-vary-with-respect-to-resistance-to-viral-infection
#10
Yonghong Liu, Yuanyuan Liu, Jiaming Wu, Bernard Roizman, Grace Guoying Zhou
Analyses of the levels of mRNAs encoding IFIT1, IFI16, RIG-1, MDA5, CXCL10, LGP2, PUM1, LSD1, STING, and IFNβ in cell lines from which the gene encoding LGP2, LSD1, PML, HDAC4, IFI16, PUM1, STING, MDA5, IRF3, or HDAC 1 had been knocked out, as well as the ability of these cell lines to support the replication of HSV-1, revealed the following: ( i ) Cell lines lacking the gene encoding LGP2, PML, or HDAC4 (cluster 1) exhibited increased levels of expression of partially overlapping gene networks. Concurrently, these cell lines produced from 5 fold to 12 fold lower yields of HSV-1 than the parental cells...
April 3, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29552370/effect-of-adalimumab-on-refractory-arthritis-in-juvenile-idiopathic-inflammatory-myopathy-with-anti-mda5-autoantibody
#11
Takako Miyamae, Takuma Hara, Aki Hanaya, Yumi Tani, Takayuki Kishi, Hisashi Yamanaka
A 10-year-old girl manifested persistent fever, skin rash, leg pain, fatigue, and joint pain. Based on muscle weakness, elevated muscle-derived enzymes, magnetic resonance imaging, and skin biopsy results, the diagnosis was juvenile idiopathic inflammatory myopathies (JIIM). Chest CT was normal; the anti-melanoma differentiation-associated protein-5 (anti-MDA5) autoantibody was positive. Initial manifestations subsided after prednisolone (PSL) and methotrexate treatment. After the PSL dosage was decreased, the patient presented with metacarpophalangeal (MCP) joint pain and swelling in both index fingers, synovial fluid, and signals on power Doppler ultrasound...
2018: Case Reports in Rheumatology
https://www.readbyqxmd.com/read/29534222/an-origin-of-the-immunogenicity-of-in-vitro-transcribed-rna
#12
Xin Mu, Emily Greenwald, Sadeem Ahmad, Sun Hur
The emergence of RNA-based therapeutics demands robust and economical methods to produce RNA with few byproducts from aberrant activity. While in vitro transcription using the bacteriophage T7 RNA polymerase is one such popular method, its transcripts are known to display an immune-stimulatory activity that is often undesirable and uncontrollable. We here showed that the immune-stimulatory activity of T7 transcript is contributed by its aberrant activity to initiate transcription from a promoter-less DNA end...
March 9, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29532710/myositis-specific-autoantibodies-in-japanese-patients-with-juvenile-idiopathic-inflammatory-myopathies
#13
Masahiro Ueki, Ichiro Kobayashi, Shunichiro Takezaki, Yusuke Tozawa, Yuka Okura, Masafumi Yamada, Masataka Kuwana, Tadashi Ariga
OBJECTIVES: The aim of our study is to clarify the association of myositis-specific autoantibodies (MSAs) with clinical and laboratory features in Japanese patients with juvenile idiopathic inflammatory myopathies (JIIMs). METHODS: We retrospectively analyzed the frequency of MSAs and their association with clinical or laboratory findings in 25 Japanese patients with JIIMs in Hokkaido district. RESULTS: Eighteen of 25 patients (72%) were positive for MSAs; seven with anti-melanoma differentiation associated gene (MDA) 5 (28%), 5 with anti-transcriptional intermediary factor (TIF)-1γ (20%), 4 with anti-MJ/nuclear matrix protein (NXP)-2 (16%), 2 with anti-Jo-1 (8%), 1 with anti- HMG-CoA reductase, 1 with anti-signal recognition peptide (SRP) antibodies (4% each), including co-existence and transition of MSAs in one patient each...
March 13, 2018: Modern Rheumatology
https://www.readbyqxmd.com/read/29529898/improved-quantification-of-a-commercial-enzyme-linked-immunosorbent-assay-kit-for-measuring-anti-mda5-antibody
#14
Takahisa Gono, Yuka Okazaki, Akihiro Murakami, Masataka Kuwana
OBJECTIVES: To compare the quantitative performance for measuring anti-MDA5 antibody titer of two enzyme-linked immunosorbent assay (ELISA) systems: an in-house ELISA and the commercial MESACUPTM anti-MDA5 test. METHODS: Anti-MDA5 antibody titer was measured in sera from 70 patients with dermatomyositis using an in-house ELISA and the MESACUPTM anti-MDA5 test side-by-side. For the commercial ELISA kit, serum samples diluted 1:101 were used according to the manufacturer's protocol, but serial dilutions of sera were also examined to identify the optimal serum dilution for quantification...
March 13, 2018: Modern Rheumatology
https://www.readbyqxmd.com/read/29525183/line1-contributes-to-autoimmunity-through-both-rig-i-and-mda5-mediated-rna-sensing-pathways
#15
Ke Zhao, Juan Du, Yanfeng Peng, Peng Li, Shaohua Wang, Yu Wang, Jingwei Hou, Jian Kang, Wenwen Zheng, Shucheng Hua, Xiao-Fang Yu
Improper host immune activation leads to the development of the autoimmune disease Aicardi-Goutières syndrome (AGS), which is attributed to defined genetic mutations in such proteins as TREX1 and ADAR1. The mechanism of immune activation in AGS patients has not been thoroughly elucidated to date. In this study, we report that endogenous LINE1 components trigger IFNβ production in multiple human cell types, including those defective for cGAS/STING-mediated DNA sensing. In these cells, LINE1 DNA synthesis and retrotransposition were not required for LINE1-triggered immune activation, but RNA sensing pathways were essential...
March 7, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29524530/hepatitis-d-virus-replication-is-sensed-by-mda5-and-induces-ifn-%C3%AE-%C3%AE-responses-in-hepatocytes
#16
Zhenfeng Zhang, Christina Filzmayer, Yi Ni, Holger Sültmann, Pascal Mutz, Marie-Sophie Hiet, Florian W R Vondran, Ralf Bartenschlager, Stephan Urban
BACKGROUND & AIMS: Hepatitis B virus (HBV) and D virus (HDV) co-infections cause the most severe form of viral hepatitis. HDV induces an innate immune response, but it is unknown how the host cell senses HDV and if this defense affects HDV replication. We aim to characterize interferon (IFN) activation by HDV, identify the responsible sensor and evaluate the effect of IFN on HDV replication. METHODS: HDV and HBV susceptible hepatoma cell lines and primary human hepatocytes (PHH) were used for infection studies...
March 7, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29512705/interferon-regulatory-factor-3-mediates-poly-i-c-induced-innate-immune-response-and-apoptosis-in-non%C3%A2-small-cell-lung-cancer
#17
Liang Yi, Dan Sun, Qian Han, Zhonghui Liu, Zeng Zeng, Yanping Wu, Xiaoyu Chai, Xinmin Liu
Immunotherapy is considered one of the most promising treatments for lung cancer. The cell signalling molecules melanoma differentiation-associated protein 5 (MDA5) and retinoic acid-inducible gene I protein (RIG‑I) are essential receptors that recognise intracellular pathogen-associated nucleic acids, whereas interferon regulatory factor 3 (IRF3) controls the expression of innate immunity-associated genes in macrophages. However, the innate immune response to polyinosinic:polycytidylic acid [Poly(I:C)] in lung cancer remains to be elucidated...
March 5, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29510252/antiviral-activity-of-transiently-expressed-mitochondrial-antiviral-signaling-adapter-mavs-orthologue-from-asian-seabass
#18
Rahul Krishnan, Jeena K, Zahoor Mushtaq, K U Shyam, Pani Prasad Kurcheti
The innate immune signaling adapter, Mitochondrial antiviral signaling protein (MAVS) coordinates the signals received from two independent RLRs (RIG-1 and MDA5) to induce IFN & interferon stimulatory genes (ISGs). In the present study, we report identification of an orthologue of MAVS from Lates calcarifer (LcMAVS) and its functional role in piscine RLR signaling. The LcMAVS-cDNA was cloned into pcDNA and transfected into SISS cells. LcMAVS was detected to be a 61KDa protein in western blot. Confocal microscopy demonstrated the mitochondrial localization of LcMAVS...
March 3, 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29509510/epicutaneous-administration-of-the-pattern-recognition-receptor-agonist-polyinosinic-polycytidylic-acid-activates-the-mda5-mavs-pathway-in-langerhans-cells
#19
Pooja Tajpara, Christopher Schuster, Elisabeth Schön, Philip Kienzl, Martin Vierhapper, Michael Mildner, Adelheid Elbe-Bürger
Together with keratinocytes (KCs) and the dense network of Langerhans cells (LCs), the epidermis is an ideal portal for vaccine delivery. Pattern recognition receptor agonists, in particular polyinosinic-polycytidylic acid [p(I:C)], are promising adjuvant candidates for therapeutic vaccination to generate protective T-cell immunity. Here we established an ex vivo skin explant model to study the expression and activation of double-stranded RNA (dsRNA)-sensing pattern recognition receptors in LCs and KCs in human skin...
March 6, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29496994/fascin1-suppresses-rig-i-like-receptor-signaling-and-interferon-%C3%AE-production-by-associating-with-i%C3%AE%C2%BAb-kinase-%C3%AF%C2%B5-ikk-%C3%AF%C2%B5-in-colon-cancer
#20
Tomio Matsumura, Shigeaki Hida, Masato Kitazawa, Chifumi Fujii, Akira Kobayashi, Michiko Takeoka, Shun-Ichiro Taniguchi, Shin-Ichi Miyagawa
Fascin1 is an actin-bundling protein involved in cancer cell migration and has recently been shown also to have roles in virus-mediated immune cell responses. Because viral infection has been shown to activate immune cells and to induce IFN-β expression in human cancer cells, we evaluated the effects of fascin1 on virus-dependent signaling via the membrane- and actin-associated protein retinoic acid-inducible gene I (RIG-I) in colon cancer cells. We knocked down fascin1 expression with shRNA retrovirally transduced into a DLD-1 colon cancer and L929 fibroblast-like cell lines and used luciferase reporter assays and co-immunoprecipitation to identify fascin1 targets...
March 1, 2018: Journal of Biological Chemistry
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