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https://www.readbyqxmd.com/read/28342759/activation-of-epithelial-stat1-by-interleukin-28-controls-mucosal-healing-in-mice-with-colitis-and-is-increased-in-mucosa-of-patients-with-inflammatory-bowel-disease
#1
Mircea T Chiriac, Barbara Buchen, Alexandra Wandersee, Gheorghe Hundorfean, Claudia Günther, Yvonne Bourjau, Sean E Doyle, Benjamin Frey, Arif B Ekici, Christian Büttner, Benno Weigmann, Raja Atreya, Stefan Wirtz, Christoph Becker, Jürgen Siebler, Markus F Neurath
BACKGROUND & AIMS: We investigated the roles of interleukin 28A (also called IL28A or interferon lambda 2) in intestinal epithelial cell (IEC) activation, studying its effects in mouse models of inflammatory bowel diseases (IBD) and intestinal mucosal healing. METHODS: Colitis was induced in C57BL/6JCrl mice (controls), mice with intestinal epithelial cell-specific disruption of Stat1 (Stat1IEC-KO), mice with disruption of the interferon lambda receptor 1 gene (Il28ra-/-), and mice with disruption of the interferon regulatory factor 3 gene (Irf3-/-), with or without disruption of Irf7 (Irf7-/-)...
March 22, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28331091/ebolaviruses-associated-with-differential-pathogenicity-induce-distinct-host-responses-in-human-macrophages
#2
Judith Olejnik, Adriana Forero, Laure R Deflubé, Adam J Hume, Whitney A Manhart, Andrew Nishida, Andrea Marzi, Michael G Katze, Hideki Ebihara, Angela L Rasmussen, Elke Mühlberger
Ebola virus (EBOV) and Reston virus (RESTV) are members of the Ebolavirus genus which greatly differ in their pathogenicity. While EBOV causes a severe disease in humans characterized by a dysregulated inflammatory response and elevated cytokine and chemokine production, there are no reported disease-associated human cases of RESTV infection, suggesting that RESTV is non-pathogenic for humans. The underlying mechanisms determining the pathogenicity of different ebolavirus species are not yet known. In this study we dissect the host response to EBOV and RESTV infection in primary human monocyte-derived macrophages (MDMs)...
March 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28302626/sting-irf3-triggers-endothelial-inflammation-in-response-to-free-fatty-acid-induced-mitochondrial-damage-in-diet-induced-obesity
#3
Yun Mao, Wei Luo, Lin Zhang, Weiwei Wu, Liangshuai Yuan, Hao Xu, Juhee Song, Keigi Fujiwara, Jun-Ichi Abe, Scott A LeMaire, Xing Li Wang, Ying H Shen
OBJECTIVE: Metabolic stress in obesity induces endothelial inflammation and activation, which initiates adipose tissue inflammation, insulin resistance, and cardiovascular diseases. However, the mechanisms underlying endothelial inflammation induction are not completely understood. Stimulator of interferon genes (STING) is an important molecule in immunity and inflammation. In the present study, we sought to determine the role of STING in palmitic acid-induced endothelial activation/inflammation...
March 16, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28295920/importin-%C3%AE-1-targeting-by-hepatitis-c-virus-ns3-4a-protein-restricts-irf3-and-nf-%C3%AE%C2%BAb-signaling-of-ifnb1-antiviral-response
#4
Bridget Gagné, Nicolas Tremblay, Alex Y Park, Martin Baril, Daniel Lamarre
In this study, newly identified host interactors of hepatitis C virus (HCV) proteins were assessed for a role in modulating innate immune response. The analysis revealed enrichment for components of the nuclear transport machinery and the crucial interaction with NS3/4A protein in suppression of interferon-β (IFNB1) induction. Using a comprehensive microscopy-based high-content screening approach combined to the gene silencing of nuclear transport factors, we showed that NS3/4A-interacting proteins control the nucleocytoplasmic trafficking of IFN regulatory factor 3 (IRF3) and NF-κB p65 upon Sendai virus (SeV) infection...
March 13, 2017: Traffic
https://www.readbyqxmd.com/read/28288804/mir-146a-potentially-promotes-ivig-mediated-inhibition-of-tlr4-signaling-in-lps-activated-human-monocytes
#5
Lionel Loubaki, Dominique Chabot, Isabelle Paré, Mathieu Drouin, Renée Bazin
IVIg is used as an immunomodulatory agent in inflammatory disorders such as sepsis. IVIg also affects monocyte differentiation and functions, two processes in which microRNAs play a crucial role. Monocytes detect microorganisms through pathogen recognition receptors (PRRs) such as TLR4. MiR-146a has been shown to supress NF-κB and IRF3 activity, two key components of TLR4 signaling. To evaluate whether miR-146a is involved in the anti-inflammatory effects of IVIg, monocytes were treated with LPS or IVIg alone or, alternately, first activated with LPS followed by washing and addition of IVIg...
March 10, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28288457/interferon-dependent-induction-of-clr-b-during-mouse-cytomegalovirus-infection-protects-bystander-cells-from-natural-killer-cells-via-nkr-p1b-mediated-inhibition
#6
Christina L Kirkham, Oscar A Aguilar, Tao Yu, Miho Tanaka, Aruz Mesci, Kuan-Lun Chu, Jason H Fine, Karen L Mossman, Rod Bremner, David S J Allan, James R Carlyle
Natural killer (NK) cells are innate lymphocytes that aid in self-nonself discrimination by recognizing cells undergoing pathological alterations. The NKR-P1B inhibitory receptor recognizes Clr-b, a self-encoded marker of cell health downregulated during viral infection. Here, we show that Clr-b loss during mouse cytomegalovirus (MCMV) infection is predicated by a loss of Clr-b (Clec2d) promoter activity and nascent transcripts, driven in part by MCMV ie3 (M122) activity. In contrast, uninfected bystander cells near MCMV-infected fibroblasts reciprocally upregulate Clr-b expression due to paracrine type-I interferon (IFN) signaling...
March 14, 2017: Journal of Innate Immunity
https://www.readbyqxmd.com/read/28286505/mda5-induces-a-stronger-interferon-response-than-rig-i-to-gcrv-infection-through-a-mechanism-involving-the-phosphorylation-and-dimerization-of-irf3-and-irf7-in-cik-cells
#7
Quanyuan Wan, Chunrong Yang, Youliang Rao, Zhiwei Liao, Jianguo Su
Retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) are critical cytosolic sensors that trigger the production of interferons (IFNs). Though their recognition functions are well identified, their unique roles in the downstream signal transduction remain to be elucidated. Herein, we report the differential effect between grass carp (Ctenopharyngodon idella) MDA5 (CiMDA5) and CiRIG-I on the production of various IFNs upon grass carp reovirus (GCRV) infection in C. idella kidney (CIK) cell line...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28283953/the-effects-of-agaricus-blazei-murill-polysaccharides-on-cadmium-induced-apoptosis-and-the-tlr4-signaling-pathway-of-peripheral-blood-lymphocytes-in-chicken
#8
Wenjing Liu, Ming Ge, Xuequan Hu, Ai Lv, Dexing Ma, Xiaodan Huang, Ruili Zhang
In this study, we investigated the effects of Agaricus blazei Murill polysaccharides (ABP) on cadmium (Cd)-induced apoptosis and the TLR4 signaling pathway of chicken peripheral blood lymphocytes (PBLs). Seven-day-old healthy chickens were randomly divided into four groups, and each group contained 20 males. The cadmium-supplemented diet group (Cd group) was fed daily with full feed that contained 140 mg cadmium chloride (CdCl2)/kg and 0.2 mL saline. The A. blazei Murill polysaccharide diet group (ABP group) was fed daily with full feed with 0...
March 10, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/28279563/a-small-molecule-irf3-agonist-functions-as-an-influenza-vaccine-adjuvant-by-modulating-the-antiviral-immune-response
#9
Peter Probst, John B Grigg, Myra Wang, Ernesto Muñoz, Yueh-Ming Loo, Renee C Ireton, Michael Gale, Shawn P Iadonato, Kristin M Bedard
Vaccine adjuvants are essential to drive a protective immune response in cases where vaccine antigens are weakly immunogenic, where vaccine antigen is limited, or where an increase in potency is needed for a specific population, such as the elderly. To discover novel vaccine adjuvants, we used a high-throughput screen (HTS) designed to identify small-molecule agonists of the RIG-I-like receptor (RLR) pathway leading to interferon regulatory factor 3 (IRF3) activation. RLRs are a group of cytosolic pattern-recognition receptors that are essential for the recognition of viral nucleic acids during infection...
March 6, 2017: Vaccine
https://www.readbyqxmd.com/read/28273337/ethanol-tlr3-and-tlr4-agonists-have-unique-innate-immune-responses-in-neuron-like-sh-sy5y-and-microglia-like-bv2
#10
Colleen J Lawrimore, Fulton T Crews
Ethanol (EtOH) consumption leads to an increase of proinflammatory signaling via activation of toll-like receptors (TLRs) such as TLR3 and TLR4 that leads to kinase activation (ERK1/2, p38, TBK1), transcription factor activation (NFκB, IRF3) and increased transcription of pro-inflammatory cytokines such as TNFα, IL-1β, and IL-6. This immune signaling cascade is thought to play a role in neurodegeneration and alcohol use disorders. While microglia are considered to be the primary macrophage in brain, it is unclear what if any role neurons play in ethanol-induced proinflammatory signaling METHODS: Microglia-like BV2 and retinoic acid differentiated neuron-like SH-SY5Y were treated with TLR3 agonist Poly(I:C), TLR4 agonist LPS, or EtOH for 10 or 30 minutes to examine proinflammatory immune signaling kinase and transcription factor activation using western blot, and for 24 hours to examine induction of proinflammatory gene mRNA using RT-PCR RESULTS: In BV2, both LPS and Poly(I:C) increased p-ERK1/2, p-p38, and p-NFκB by 30 minutes, whereas EtOH decreased p-ERK1/2 and increased p-IRF3...
March 8, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28273161/the-e3-ubiquitin-ligase-rnf185-facilitates-the-cgas-mediated-innate-immune-response
#11
Qiang Wang, Liyuan Huang, Ze Hong, Zhongshi Lv, Zhaomin Mao, Yijun Tang, Xiufang Kong, Senlin Li, Ye Cui, Heng Liu, Lele Zhang, Xiaojie Zhang, Lindi Jiang, Chen Wang, Qin Zhou
The cyclic GMP-AMP synthase (cGAS), upon cytosolic DNA stimulation, catalyzes the formation of the second messenger 2'3'-cGAMP, which then binds to stimulator of interferon genes (STING) and activates downstream signaling. It remains to be elucidated how the cGAS enzymatic activity is modulated dynamically. Here, we reported that the ER ubiquitin ligase RNF185 interacted with cGAS during HSV-1 infection. Ectopic-expression or knockdown of RNF185 respectively enhanced or impaired the IRF3-responsive gene expression...
March 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28258480/the-anti-hsv-1-effect-of-quercetin-is-dependent-on-the-suppression-of-tlr-3-in-raw-264-7-cells
#12
Seulki Lee, Hwan Hee Lee, Yu Su Shin, Hyojeung Kang, Hyosun Cho
Quercetin is a major component of the plant Glycyrrhiza uralensis, which is largely used as a traditional medicine in Asia. Quercetin has been reported to have several biological activities, which include anti-viral and anti-inflammatory effects. We explored the molecular mechanism linking anti-viral and anti-inflammatory activities using an in vitro herpes simplex virus-1 (HSV-1) infection model. Raw 264.7 cells were infected with HSV-1 in the presence or absence of different concentrations of quercetin and infected cell lysates were harvested 24 h later...
March 3, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28228554/association-of-lyn-kinase-with-membrane-rafts-determines-its-negative-influence-on-lps-induced-signaling
#13
Kinga Borzęcka-Solarz, Justyna Dembińska, Aneta Hromada-Judycka, Gabriela Traczyk, Anna Ciesielska, Ewelina Ziemlińska, Anna Świątkowska, Katarzyna Kwiatkowska
Lipopolysaccharide (LPS) is the component of Gram-negative bacteria which activates Toll-like receptor 4 (TLR4) to trigger pro-inflammatory responses. We examined the involvement of Lyn tyrosine kinase in TLR4 signaling of macrophages, distinguishing its catalytic activity and intermolecular interactions. For this, a series of Lyn-GFP constructs bearing point mutations in particular domains of Lyn were overexpressed in RAW264 macrophage-like cells or murine peritoneal macrophages, and their influence on LPS-induced responses was analyzed...
February 22, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28199372/endometrial-factors-similarly-induced-by-ifnt2-and-ifntc1-through-transcription-factor-foxs1
#14
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/28197148/avian-interferons-and-their-antiviral-effectors
#15
REVIEW
Diwakar Santhakumar, Dennis Rubbenstroth, Luis Martinez-Sobrido, Muhammad Munir
Interferon (IFN) responses, mediated by a myriad of IFN-stimulated genes (ISGs), are the most profound innate immune responses against viruses. Cumulatively, these IFN effectors establish a multilayered antiviral state to safeguard the host against invading viral pathogens. Considerable genetic and functional characterizations of mammalian IFNs and their effectors have been made, and our understanding on the avian IFNs has started to expand. Similar to mammalian counterparts, three types of IFNs have been genetically characterized in most avian species with available annotated genomes...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28195391/rig-i-is-a-key-antiviral-interferon-stimulated-gene-against-hepatitis-e-virus-dispensable-of-interferon-production
#16
Lei Xu, Wenshi Wang, Yunlong Li, Xinying Zhou, Yuebang Yin, Yijin Wang, Robert A de Man, Luc J W van der Laan, Fen Huang, Nassim Kamar, Maikel P Peppelenbosch, Qiuwei Pan
Interferons (IFNs) are broad antiviral cytokines that exert their function by inducing the transcription of hundreds of interferon-stimulated genes (ISGs). However, little is known about the antiviral potential of these cellular effectors on hepatitis E virus (HEV) infection, the leading cause of acute hepatitis globally. In this study, we profiled the antiviral potential of a panel of important human ISGs on HEV replication in cell culture models by overexpression of individual ISG. The mechanism-of-action of the key anti-HEV ISG was further studied...
February 13, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28192879/knockdown-of-irf3-inhibits-extracellular-matrix-expression-in-keloid-fibroblasts
#17
Yi Zhang, Li Zhang, Xiao-Hua Lin, Zhi-Ming Li, Qi-Yu Zhang
Keloid is a pathologic fibro-proliferative disorder and is characterized by hyper-proliferation of fibroblasts and excess extracellular matrix (ECM) deposition. Interferon regulatory factor 3 (IRF3) is a member of the interferon-regulatory factor (IRF) family and has been shown to play a critical modulator in the progression of fibrosis. However, the function of IRF3 in dermal fibrosis remains unclear. Thus, in this study, we investigated the effects of IRF3 on keloid-derived fibroblasts (KFs) proliferation and ECM expression, and explored the underlying mechanism...
April 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28188292/cytosolic-dna-promotes-signal-transducer-and-activator-of-transcription-3-stat3-phosphorylation-by-tank-binding-kinase-1-tbk1-to-restrain-stat3-activity
#18
Hung-Ching Hsia, Jessica E Hutti, Albert S Baldwin
Cytosolic DNA can elicit beneficial as well as undesirable immune responses. For example, viral or microbial DNA triggers cell-intrinsic immune responses to defend against infections, whereas aberrant cytosolic accumulation of self-DNA results in pathological conditions, such as autoimmunity. Given the importance of these DNA-provoked responses, a better understanding of their molecular mechanisms is needed. Cytosolic DNA engages stimulator of interferon genes (STING) to activate TANK-binding kinase 1 (TBK1), which subsequently phosphorylates the transcription factor interferon regulatory factor 3 (IRF3) to promote interferon expression...
February 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28181039/irf3-inhibits-neutrophil-recruitment-in-mice-infected-with-pseudomonas-aeruginosa
#19
Zhenghao Piao, Haiying Yuan, Cuili Wang, Liyun Shi
Pseudomonas aeruginosa is the major cause of morbidity and mortality in patients with ventilator-associated pneumonia. Interferon regulatory factor 3 (IRF3) is a transcription factor that plays an important role in the immune response to viral infection via the IRF3/IFN-β signaling pathway. Controversial data exist regarding the role of IRF3 in immune cell recruitment during bacterial infections. IRF3 has been shown to promote neutrophil recruitment and bacterial clearance in mice infected with P. aeruginosa by inducing the production of specific chemokines and cytokines...
February 8, 2017: Inflammation
https://www.readbyqxmd.com/read/28179530/japanese-encephalitis-virus-ns5-inhibits-the-type-i-interferon-production-by-blocking-the-nuclear-translocation-of-irf3-and-nf-%C3%AE%C2%BAb
#20
Jing Ye, Zheng Chen, Yunchuan Li, Zikai Zhao, Wen He, Ali Zohaib, Yunfeng Song, Chenglin Deng, Bo Zhang, Huanchun Chen, Shengbo Cao
The type I interferon (IFN) response is part of a first-line defense against viral infection. To initiate replication, viruses have developed powerful evasion strategies to counteract host IFN responses. In present study, we found that Japanese encephalitis virus (JEV) NS5 protein could inhibit double strand RNA (dsRNA)-induced IFN-β expression in a dose-dependent manner. Our data further demonstrated that JEV NS5 suppressed the activation of IFN transcriptional factors, IRF3 and NF-κB. However, there was no defect in the phosphorylation of IRF3 and degradation of IκB, an upstream inhibitor of NF-κB, upon NS5 expression, indicating a direct inhibition of the nuclear localization of IRF3 and NF-κB by NS5...
February 8, 2017: Journal of Virology
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