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https://www.readbyqxmd.com/read/29774490/higher-activation-of-the-interferon-gamma-signaling-pathway-in-systemic-lupus-erythematosus-patients-with-a-high-type-i-ifn-score-relation-to-disease-activity
#1
Manman Liu, Junli Liu, Shumeng Hao, Ping Wu, Xiaoyan Zhang, Yichuan Xiao, Gengru Jiang, Xinfang Huang
Increased IFN-γ levels have been associated with systemic lupus erythematosus (SLE). However, the relationships among IFN-γ, type I interferons (IFNs) and clinical features have not been extensively studied. Peripheral blood samples from 44 SLE patients and 36 healthy donors (HDs) were collected. Quantitative real-time PCR was used to assess the mRNA expression of IFNG, type II IFN-inducible genes (IRF1, GBP1, CXCL9, CXCL10, and SERPING1, which are used for the type II IFN score), type I IFN-inducible genes (IRF7, MX1, ISG15, and ISG20, which are used for the type I IFN score), TBX21, and EOMES in peripheral blood mononuclear cells...
May 17, 2018: Clinical Rheumatology
https://www.readbyqxmd.com/read/29755463/the-role-of-optineurin-in-antiviral-type-i-interferon-production
#2
REVIEW
Ahmed Outlioua, Marie Pourcelot, Damien Arnoult
After a viral infection and the stimulation of some pattern-recognition receptors as the toll-like receptor 3 in the endosomes or the RIG-I-like receptors in the cytosol, activation of the IKK-related kinase TBK1 leads to the production of type I interferons (IFNs) after phosphorylation of the transcription factors IRF3 and IRF7. Recent findings indicate an involvement of K63-linked polyubiquitination and of the Golgi-localized protein optineurin (OPTN) in the activation of this crucial kinase involved in innate antiviral immunity...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29742479/flaviviridae-virus-nonstructural-proteins-5-and-5a-mediate-viral-immune-evasion-and-are-promising-targets-in-drug-development
#3
REVIEW
Shun Chen, Chao Yang, Wei Zhang, Suresh Mahalingam, Mingshu Wang, Anchun Cheng
Infections with viruses in the Flaviviridae family have a vast global and economic impact because of the high morbidity and mortality. The pathogenesis of Flaviviridae infections is very complex and not fully understood because these viruses can inhibit multiple immune pathways including the complement system, NK cells, and IFN induction and signalling pathways. The non-structural (NS) 5 and 5A proteins of Flaviviridae viruses are highly conserved and play an important role in resisting host immunity through various evasion mechanisms...
May 6, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29727627/differential-interferon-system-gene-expression-profiles-in-susceptible-and-resistant-gynogenetic-clones-of-gibel-carp-challenged-with-herpesvirus-cahv
#4
Cheng-Yan Mou, Yang Wang, Qi-Ya Zhang, Fan-Xiang Gao, Zhi Li, Jin-Feng Tong, Li Zhou, Jian-Fang Gui
Interferon (IFN) system plays a vital role in the first line of defense against viruses. In this study, we first identified multiple transcripts of 15 IFN system genes, including PRRs (TLR2, TLR3, RIG-I, and LGP2), PRR-mediated IFN signal pathway (MyD88, MITA, and MAVS), IFN regulatory factors (IRF1, IRF3, IRF7, and IRF9), IFNs (IFNφ1 and IFNφ3), and ISGs (Mx and viperin), and one transcript of TLR9 in de novo transcriptome assembly data of gibel carp head-kidney. Multiple nucleotide alignments and phylogenetic analysis of common region showed that the transcripts of every of the 15 IFN system genes were classified into two homologs with distinctly divergent sequences, indicating that hexaploid gibel carp may be an allopolyploid...
May 1, 2018: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29720400/interferon-regulatory-factor-1-and-a-variant-of-heterogeneous-nuclear-ribonucleoprotein-l-coordinately-silence-the-gene-for-adhesion-protein-ceacam1
#5
Kenneth J Dery, Craig Silver, Lu Yang, John E Shively
The adhesion protein Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is widely expressed in epithelial cells as a short cytoplasmic isoform (S-iso) and in leukocytes as a long cytoplasmic isoform (L-iso) and is frequently silenced in cancer by unknown mechanisms. Previously, we reported that interferon response factor 1 (IRF1) biases alternative splicing (AS) to include the variable exon 7 in CEACAM1, generating L-iso. We now show that IRF1 and a variant of heterogeneous nuclear ribonucleoprotein L (Lv1) coordinately silence the CEACAM1 gene...
May 2, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29717061/the-interaction-between-ikk%C3%AE-and-lc3-promotes-type-i-interferon-production-through-the-tlr9-containing-laposome
#6
Kachiko Hayashi, Manabu Taura, Akiko Iwasaki
Toll-like receptor 9 (TLR9) recognizes DNA in endosomes and activates distinct signaling pathways to stimulate the production of proinflammatory cytokines and type I interferons (IFNs). The assembly of signaling platforms on microtubule-associated proteins 1A/1B-light chain 3 (LC3)-decorated endosomal vesicles is required to transduce TLR9 signals that stimulate the production of IFN but not interleukin-12 p40 (IL-12p40). LC3-associated phagocytosis (LAP), a form of noncanonical autophagy, is critical for the activation of interferon regulatory factor 7 (IRF7) and for IFN synthesis...
May 1, 2018: Science Signaling
https://www.readbyqxmd.com/read/29712772/socs1-and-socs3-target-irf7-degradation-to-suppress-tlr7-mediated-type-i-ifn-production-of-human-plasmacytoid-dendritic-cells
#7
Chun-Feng Yu, Wen-Ming Peng, Martin Schlee, Winfried Barchet, Anna Maria Eis-Hübinger, Waldemar Kolanus, Matthias Geyer, Sebastian Schmitt, Folkert Steinhagen, Johannes Oldenburg, Natalija Novak
Type I IFN production of plasmacytoid dendritic cells (pDCs) triggered by TLR-signaling is an essential part of antiviral responses and autoimmune reactions. Although it was well-documented that members of the cytokine signaling (SOCS) family regulate TLR-signaling, the mechanism of how SOCS proteins regulate TLR7-mediated type I IFN production has not been elucidated yet. In this article, we show that TLR7 activation in human pDCs induced the expression of SOCS1 and SOCS3. SOCS1 and SOCS3 strongly suppressed TLR7-mediated type I IFN production...
April 30, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29698503/gene-expression-profiles-of-immune-regulatory-genes-in-whole-blood-of-cattle-with-a-subclinical-infection-of-mycobacterium-avium-subsp-paratuberculosis
#8
Hyun-Eui Park, Hong-Tae Park, Young Hoon Jung, Han Sang Yoo
Johne's disease is a chronic wasting disease of ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP), resulting in inflammation of intestines and persistent diarrhea. The initial host response against MAP infections is mainly regulated by the Th1 response, which is characterized by the production of IFN-γ. With the progression of disease, MAP can survive in the host through the evasion of the host's immune response by manipulating the host immune response. However, the host response during subclinical phases has not been fully understood...
2018: PloS One
https://www.readbyqxmd.com/read/29681974/baicalin-downregulates-rlrs-signaling-pathway-to-control-influenza-a-virus-infection-and-improve-the-prognosis
#9
Peng Pang, Ke Zheng, Sizhi Wu, Huachong Xu, Li Deng, Yucong Shi, Xiaoyin Chen
The objective of this study is to investigate the effects of baicalin on controlling the pulmonary infection and improving the prognosis in influenza A virus (IAV) infection. PCR and western blot were used to measure the changes of some key factors in RLRs signaling pathway. MSD electrochemiluminescence was used to measure the expression of pulmonary inflammatory cytokines including IFN- γ , TNF- α , IL-1 β , IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, and KC/GRO. Flow cytometry was used to detect the proportion of Th1, Th2, Th17, and Treg...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29673738/tbk1-a-key-regulator-and-potential-treatment-target-for-interferon-positive-sj%C3%A3-gren-s-syndrome-systemic-lupus-erythematosus-and-systemic-sclerosis
#10
Iris L A Bodewes, Erika Huijser, Cornelia G van Helden-Meeuwsen, Liselotte Tas, Ruth Huizinga, Virgil A S H Dalm, P Martin van Hagen, Noortje Groot, Sylvia Kamphuis, Paul L A van Daele, Marjan A Versnel
OBJECTIVE: Upregulation of type I interferons (IFN-I) is a hallmark of systemic autoimmune diseases like primary Sjögren's syndrome (pSS), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). Expression of IFN-I is induced by three different receptor families: Toll-like receptors (TLRs), RIG-like receptors (RLRs) and DNA-sensing receptors (DSRs). TANK-binding kinase (TBK1) is an important signaling hub downstream of RLRs and DSRs. TBK1 activates IRF3 and IRF7, leading to IFN-I production and subsequent induction of interferon stimulated genes (ISGs)...
April 16, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29619666/effectiveness-of-different-avian-influenza-h5-vaccination-regimens-in-layer-chickens-on-the-humoral-immune-response-and-interferon-alpha-signalling-immune-marker
#11
Mustafa Hamad, Omar Amen, Mohamed Mahmoud, Ola Hassanin, Mostafa Saif-Edin
Avian influenza (AI) vaccines are widely used to control and eliminate the ongoing avian influenza virus epidemic in Egypt. A strict vaccination policy with inactivated AI vaccines has been widely applied, however the virus still circulating, evolving and causing great negative impact to the poultry sector in Egypt. Therefore, an updated poultry vaccination policy using different vaccine technologies might be valuable as an innovative additional control strategy of AIV in Egypt. In the present study, the effectiveness of different avian influenza (AI) vaccination schedules was evaluated in 300 commercial layer chicks (ISA White) using either the oil-emulsion baculovirus-H5-prototype vaccine (baculovirus-H5 prototype) or turkey herpesvirus (HVT) vector vaccine containing the hemagglutinin (HA) gene from H5N1 strain (rHVT-H5), applied alone or in combination and in different settings...
April 4, 2018: Veterinary Research Communications
https://www.readbyqxmd.com/read/29610295/samhd1-suppresses-innate-immune-responses-to-viral-infections-and-inflammatory-stimuli-by-inhibiting-the-nf-%C3%AE%C2%BAb-and-interferon-pathways
#12
Shuliang Chen, Serena Bonifati, Zhihua Qin, Corine St Gelais, Karthik M Kodigepalli, Bradley S Barrett, Sun Hee Kim, Jenna M Antonucci, Katherine J Ladner, Olga Buzovetsky, Kirsten M Knecht, Yong Xiong, Jacob S Yount, Denis C Guttridge, Mario L Santiago, Li Wu
Sterile alpha motif and HD-domain-containing protein 1 (SAMHD1) blocks replication of retroviruses and certain DNA viruses by reducing the intracellular dNTP pool. SAMHD1 has been suggested to down-regulate IFN and inflammatory responses to viral infections, although the functions and mechanisms of SAMHD1 in modulating innate immunity remain unclear. Here, we show that SAMHD1 suppresses the innate immune responses to viral infections and inflammatory stimuli by inhibiting nuclear factor-κB (NF-κB) activation and type I interferon (IFN-I) induction...
April 2, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29604449/the-mechanisms-of-ag85a-dna-vaccine-activates-rna-sensors-through-new-signal-transduction
#13
Jingbo Zhai, Qiubo Wang, Yunfeng Gao, Ran Zhang, Shengjun Li, Bing Wei, Yong You, Xun Sun, Changlong Lu
Low immunogenicity is one of the major problems limiting the clinical use for DNA vaccines, which makes it impossible to obtain a strong protective immune response after vaccination. In order to explore whether Ag85A DNA vaccine could mount more efficiently protective immune response through new RNA sensor and its signal transduction pathway of antigen presentation we designed and synthesized Ag85A gene fragment containing multiple points mutations and transfected the gene fragment into the dendritic cell line (DC2...
March 28, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29570417/reduction-of-marek-s-disease-virus-infection-by-toll-like-receptor-ligands-in-chicken-embryo-fibroblast-cells
#14
Jegarubee Bavananthasivam, Raveendra R Kulkarni, Leah Read, Shayan Sharif
Evolutionarily conserved pattern recognition receptors, including Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns (PAMPs) that are present in microbes. PAMPs induce several pathways downstream of TLRs that lead to induction of antiviral responses. The objective of this study was to investigate the stimulatory effect of various PAMPs (in the form of TLR ligands) in reducing Marek's disease virus (MDV) infection in chicken embryo fibroblast cells (CEFs). To this end, CEFs were pretreated with Pam3CSK4, Poly(IC), lipopolysaccharide (LPS), and CpG ODN as TLR2, TLR3, TLR4, and TLR21 ligands, respectively for 24 h followed by infection with MDV...
March 23, 2018: Viral Immunology
https://www.readbyqxmd.com/read/29538462/role-of-toll-like-receptors-and-interferon-regulatory-factors-in-different-experimental-heart-failure-models-of-diverse-etiology-irf7-as-novel-cardiovascular-stress-inducible-factor
#15
Peter Moritz Becher, Svenja Hinrichs, Nina Fluschnik, Jan K Hennigs, Karin Klingel, Stefan Blankenberg, Dirk Westermann, Diana Lindner
Heart failure (HF) is a leading cause of morbidity and mortality in the western world. Although optimal medical care and treatment is widely available, the prognosis of patients with HF is still poor. Toll-like receptors (TLRs) are important compartments of the innate immunity. Current studies have identified TLRs as critical mediators in cardiovascular diseases. In the present study, we investigated the involvement of TLRs and interferon (IFN) regulatory factors (IRFs) in different experimental HF models including viral myocarditis, myocardial ischemia, diabetes mellitus, and cardiac hypertrophy...
2018: PloS One
https://www.readbyqxmd.com/read/29521144/in-vitro-marker-gene-expression-analyses-in-human-peripheral-blood-mononuclear-cells-a-tool-to-assess-safety-of-influenza-vaccines-in-humans
#16
Eita Sasaki, Haruka Momose, Yuki Hiradate, Ken J Ishii, Takuo Mizukami, Isao Hamaguchi
Vaccines are inoculated in healthy individuals from children to the elderly, and thus high levels of safety and consistency of vaccine quality in each lot must meet the required specifications by using preclinical and lot release testing. Because vaccines are inoculated into humans, recapitulation of biological reactions in humans should be considered for test methods. We have developed a new method to evaluate the safety of influenza vaccines using biomarker gene expression in mouse and rat models. Some biomarker genes are already known to be expressed in human lymphocytes, macrophages and dendritic cells; therefore, we considered some of these genes might be common biomarkers for human and mice to evaluate influenza vaccine safety...
December 2018: Journal of Immunotoxicology
https://www.readbyqxmd.com/read/29515574/human-intestinal-epithelial-cells-release-antiviral-factors-that-inhibit-hiv-infection-of-macrophages
#17
Le Guo, Xi-Qiu Xu, Li Zhou, Run-Hong Zhou, Xu Wang, Jie-Liang Li, Jin-Biao Liu, Hang Liu, Biao Zhang, Wen-Zhe Ho
As a rich source of CD4+ T cells and macrophages, the gastrointestinal (GI) tract is a major target site for HIV infection. The interplay between GI-resident macrophages and intestinal epithelial cells (IECs) constitutes an important element of GI innate immunity against pathogens. In this study, we investigated whether human IECs have the ability to produce antiviral factors that can inhibit HIV infection of macrophages. We demonstrated that IECs possess functional toll-like receptor 3 (TLR3), the activation of which resulted in induction of key interferon (IFN) regulatory factors (IRF3 and IRF7), IFN-β, IFN-λ, and CC chemokines (MIP-1α, MIP-1β, RANTES), the ligands of HIV entry co-receptor CCR5...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29504848/signalling-pathways-identified-in-salivary-glands-from-primary-sj%C3%A3-gren-s-syndrome-patients-reveal-enhanced-adipose-tissue-development
#18
Lara A Aqrawi, Janicke Liaaen Jensen, Gunnvor Øijordsbakken, Ann-Kristin Ruus, Ståle Nygård, Marit Holden, Roland Jonsson, Hilde Kanli Galtung, Kathrine Skarstein
A characteristic feature of primary Sjögren's syndrome (pSS) is the destruction of salivary and lacrimal glands mediated by mononuclear cell infiltration. Adipocytes can also occupy a large portion of the salivary gland (SG) tissue area, although little is known about their significance in pSS. We have previously investigated adipose tissue infiltration in SG biopsies from pSS patients and non-SS sicca controls. Our findings indicated the distinct incidence of adipose tissue replacement in pSS patients, where adipocytes were detected in interleukin (IL) 6 rich regions...
May 2018: Autoimmunity
https://www.readbyqxmd.com/read/29463066/oasl1-traps-viral-rnas-in-stress-granules-to-promote-antiviral-responses
#19
Ji-Seon Kang, Yune-Sahng Hwang, Lark Kyun Kim, Sujung Lee, Wook-Bin Lee, Jeongsil Kim-Ha, Young-Joon Kim
Oligoadenylate synthetase (OAS) protein family is the major interferon (IFN)-stimulated genes responsible for the activation of RNase L pathway upon viral infection. OAS-like (OASL) is also required for inhibition of viral growth in human cells, but the loss of one of its mouse homolog, OASL1, causes a severe defect in termination of type I interferon production. To further investigate the antiviral activity of OASL1, we examined its subcellular localization and regulatory roles in IFN production in the early and late stages of viral infection...
March 31, 2018: Molecules and Cells
https://www.readbyqxmd.com/read/29456540/kallikrein-kinin-system-suppresses-type-i-interferon-responses-a-novel-pathway-of-interferon-regulation
#20
Alecia Seliga, Michael Hweemoon Lee, Nicole C Fernandes, Viviana Zuluaga-Ramirez, Marta Didukh, Yuri Persidsky, Raghava Potula, Stefania Gallucci, Uma Sriram
The Kallikrein-Kinin System (KKS), comprised of kallikreins (klks), bradykinins (BKs) angiotensin-converting enzyme (ACE), and many other molecules, regulates a number of physiological processes, including inflammation, coagulation, angiogenesis, and control of blood pressure. In this report, we show that KKS regulates Type I IFN responses, thought to be important in lupus pathogenesis. We used CpG (TLR9 ligand), R848 (TLR7 ligand), or recombinant IFN-α to induce interferon-stimulated genes (ISGs) and proteins, and observed that this response was markedly diminished by BKs, klk1 (tissue kallikrein), or captopril (an ACE inhibitor)...
2018: Frontiers in Immunology
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