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Interferon promoter stimulator

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https://www.readbyqxmd.com/read/28542326/the-murine-cytomegalovirus-m35-protein-antagonizes-type-i-ifn-induction-downstream-of-pattern-recognition-receptors-by-targeting-nf-%C3%AE%C2%BAb-mediated-transcription
#1
Baca Chan, Vladimir Gonçalves Magalhães, Niels A W Lemmermann, Vanda Juranić Lisnić, Markus Stempel, Kendra A Bussey, Elisa Reimer, Jürgen Podlech, Stefan Lienenklaus, Matthias J Reddehase, Stipan Jonjić, Melanie M Brinkmann
The type I interferon (IFN) response is imperative for the establishment of the early antiviral immune response. Here we report the identification of the first type I IFN antagonist encoded by murine cytomegalovirus (MCMV) that shuts down signaling following pattern recognition receptor (PRR) sensing. Screening of an MCMV open reading frame (ORF) library identified M35 as a novel and strong negative modulator of IFNβ promoter induction following activation of both RNA and DNA cytoplasmic PRR. Additionally, M35 inhibits the proinflammatory cytokine response downstream of Toll-like receptors (TLR)...
May 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28533548/lack-of-inflammatory-gene-expression-in-bats-a-unique-role-for-a-transcription-repressor
#2
Arinjay Banerjee, Noreen Rapin, Trent Bollinger, Vikram Misra
In recent years viruses similar to those that appear to cause no overt disease in bats have spilled-over to humans and other species causing serious disease. Since pathology in such diseases is often attributed to an over-active inflammatory response, we tested the hypothesis that bat cells respond to stimulation of their receptors for viral ligands with a strong antiviral response, but unlike in human cells, the inflammatory response is not overtly activated. We compared the response of human and bat cells to poly(I:C), a viral double-stranded RNA surrogate...
May 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28528914/systemic-sclerosis-dermal-fibroblasts-suppress-th1-cytokine-production-via-galectin-9-overproduction-due-to-fli1-deficiency
#3
Ryosuke Saigusa, Yoshihide Asano, Kouki Nakamura, Megumi Hirabayashi, Shunsuke Miura, Takashi Yamashita, Takashi Taniguchi, Yohei Ichimura, Takehiro Takahashi, Ayumi Yoshizaki, Tomomitsu Miyagaki, Makoto Sugaya, Shinichi Sato
Dermal fibroblasts promote skin-localized transdifferentiation of Tregs to Th2-like cells in systemic sclerosis (SSc). However, the entire effect of SSc dermal fibroblasts on immune cells still remains unknown. Since galectin-9 induces Th2 cytokine-predominant immune imbalance by negatively regulating Th1/Th17 cells in inflammatory diseases, we investigated the contribution of galectin-9 to Th immune balance in SSc lesional skin. We utilized human clinical samples and Fli1(+/-) mice because Fli1 deficiency induces SSc-like phenotypes in various cell types...
May 18, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28526557/the-frog-skin-host-defense-peptide-frenatin-2-1s-enhances-recruitment-activation-and-tumoricidal-capacity-of-nk-cells
#4
Jelena M Pantic, Ivan P Jovanovic, Gordana D Radosavljevic, Nevena M Gajovic, Nebojsa N Arsenijevic, J Michael Conlon, Miodrag L Lukic
Frog skin is a source of peptides with various biological properties. Frenatin 2.1S, derived from norepinephrine-stimulated skin secretions of the Orinoco lime tree frog Sphaenorhynchus lacteus, exhibits immunostimulatory effects as demonstrated by the promotion of proinflammatory phenotypes of mononuclear cells in mouse peritoneal cavity and spleen. The aim of this study was to identify the populations of host cells sensitive to the action of frenatin 2.1S in vivo and to study its effects on their functional antitumor capacity...
May 16, 2017: Peptides
https://www.readbyqxmd.com/read/28522827/involvement-of-gata1-and-sp3-in-the-activation-of-the-murine-sting-gene-promoter-in-nih3t3-cells
#5
Yan-Yan Xu, Rui Jin, Guo-Ping Zhou, Hua-Guo Xu
Stimulator of Interferon Gene (STING) is a key mediator of innate immune signaling. STING plays a pivotal role in the pathogenesis of many diseases including infectious diseases, auto-immune diseases and cancer. Many studies have been carried out recently in the field of STING-regulated pathway, however, rarely of transcriptional mechanisms. To characterize the murine STING (mSTING) promoter, we cloned a series of different nucleotide sequences of the 5'-flanking region of the mSTING gene. Transient transfection of promoter-reporter recombinant plasmids and luciferase assay illustrated the region (-77/+177) relative to the transcription start site (TSS) of the mSTING gene was sufficient for full promoter activity...
May 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28507789/calreticulin-promotes-immunity-and-type-i-interferon-dependent-survival-in-mice-with-acute-myeloid-leukemia
#6
Xiufen Chen, Dominick Fosco, Douglas E Kline, Justin Kline
Exposure of cancer cells to particular chemotherapeutic agents or γ-irradiation induces a form of cell death that stimulates an immune response in mice. This "immunogenic cell death" requires calreticulin (CRT) translocation to the plasma membrane, which has been shown to promote cancer cell phagocytosis. However, it remains unclear whether the effect of CRT on cancer cell phagocytosis is alone sufficient to affect tumor immunity. Acute myeloid leukemia (AML) cells expressing cell-surface CRT were generated in order to characterize the mechanism(s) through which CRT activates tumor immune responses...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28500614/irf9-stat2-fusion-protein-as-an-innate-immune-inducer-to-activate-mx-and-interferon-stimulated-gene-expression-in-zebrafish-larvae
#7
Chang-Jen Huang, Chih-Ming Chou, Huang-Wei Lien, Cheng-Ying Chu, Jhih-Yun Ho, Yimin Wu, Chia-Hsiung Cheng
Virus infection often causes large amounts of mortality during teleost larvae stage. Strong induction of innate immunity to increase survival rates of teleost larvae has been less reported. In this study, we present a zebrafish IRF9-Stat2 fusion protein (zIRF9-S2C) as a strong innate immunity inducer and characterized induction of interferon-stimulated genes (ISGs) in zebrafish larvae. zIRF9-S2C could mimic IFN-stimulated gene factor 3 (ISGF3) complex to constitutively activate transcription of Mx promoter through IFN-stimulatory element (ISRE) sites...
May 12, 2017: Marine Biotechnology
https://www.readbyqxmd.com/read/28499943/molecular-cloning-transcriptional-profiling-and-subcellular-localization-of-signal-transducer-and-activator-of-transcription-2-stat2-ortholog-from-rock-bream-oplegnathus-fasciatus
#8
S D N K Bathige, Navaneethaiyer Umasuthan, Thanthrige Thiunuwan Priyathilaka, William Shanthakumar Thulasitha, J D H E Jayasinghe, Qiang Wan, Bo-Hye Nam, Jehee Lee
Signal transducer and activator of transcription 2 (STAT2) is a key element that transduces signals from the cell membrane to the nucleus via the type I interferon-signaling pathway. Although the structural and functional aspects of STAT proteins are well studied in mammals, information on teleostean STATs is very limited. In this study, a STAT paralog, which is highly homologous to the STAT2 members, was identified from a commercially important fish species called rock bream and designated as RbSTAT2. The RbSTAT2 gene was characterized at complementary DNA (cDNA) and genomic sequence levels, and was found to possess structural features common with its mammalian counterparts...
May 9, 2017: Gene
https://www.readbyqxmd.com/read/28497030/fda-approved-immunosuppressants-targeting-staphylococcal-superantigens-mechanisms-and-insights
#9
REVIEW
Teresa Krakauer
Immunostimulating staphylococcal enterotoxin B (SEB) and related superantigenic toxins cause diseases in human beings and laboratory animals by hyperactivating cells of the immune system. These protein toxins bind to the major histocompatibility complex class II (MHC II) molecules and specific Vβ regions of T-cell receptors (TCRs), resulting in the stimulation of both monocytes/macrophages and T lymphocytes. The bridging of TCR with MHC II molecules by superantigens triggers intracellular signaling cascades, resulting in excessive release of proinflammatory mediators and massive polyclonal T-cell proliferation...
2017: ImmunoTargets and Therapy
https://www.readbyqxmd.com/read/28496530/assessment-of-the-relation-between-snp-in-mxa-gene-and-the-responsiveness-of-egyptian-hcv-genotype-4-patients-to-pegylated-interferon-and-ribavirin-treatment
#10
Mohamed Hassany, Amany Gamal, Nashwa Zaki, Basem Eysa
BACKGROUND: Pegylated interferon (PegIFN) is used in the treatment of chronic hepatitis C virus (HCV) patients especially in resource limited countries. Treatment with PegIFN stimulates the expression of a number of host genes encoding enzymes with antiviral activities, including myxovirus resistance gene-A (MxA gene). MxA gene was found to have a single nucleotide polymorphism (SNP) at position -88 in the promoter region that affects the expression of MxA gene protein and was suggested to affect the treatment outcome...
April 2017: Gastroenterology Research
https://www.readbyqxmd.com/read/28494243/a-rab20-dependent-membrane-trafficking-pathway-controls-m-%C3%A2-tuberculosis-replication-by-regulating-phagosome-spaciousness-and-integrity
#11
Laura Schnettger, Angela Rodgers, Urska Repnik, Rachel P Lai, Gang Pei, Martijn Verdoes, Robert J Wilkinson, Douglas B Young, Maximiliano G Gutierrez
The intracellular pathogen Mycobacterium tuberculosis (Mtb) lives within phagosomes and also disrupts these organelles to access the cytosol. The host pathways and mechanisms that contribute to maintaining Mtb phagosome integrity have not been investigated. Here, we examined the spatiotemporal dynamics of Mtb-containing phagosomes and identified an interferon-gamma-stimulated and Rab20-dependent membrane trafficking pathway in macrophages that maintains Mtb in spacious proteolytic phagolysosomes. This pathway functions to promote endosomal membrane influx in infected macrophages, and is required to preserve Mtb phagosome integrity and control Mtb replication...
May 10, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28487237/cytokines-affecting-cd4-t-regulatory-cells-in-transplant-tolerance-ii-interferon-gamma-ifn-%C3%AE-promotes-survival-of-alloantigen-specific-cd4-t-regulatory-cells
#12
Masaru Nomura, Suzanne J Hodgkinson, Giang T Tran, Nirupama D Verma, Catherine Robinson, Karren M Plain, Rochelle Boyd, Bruce M Hall
CD4(+)T cells that transfer alloantigen-specific transplant tolerance are short lived in culture unless stimulated with specific-donor alloantigen and lymphocyte derived cytokines. Here, we examined if IFN-γ maintained survival of tolerance transferring CD4(+)T cells. Alloantigen-specific transplant tolerance was induced in DA rats with heterotopic adult PVG heart allografts by a short course of immunosuppression and these grafts functioned for >100days with no further immunosuppression. In previous studies, we found the CD4(+)T cells from tolerant rats that transfer tolerance to an irradiated DA host grafted with a PVG heart, lose their tolerance transferring ability after 3days of culture, either with or without donor alloantigen, and effect rejection of specific-donor grafts...
May 6, 2017: Transplant Immunology
https://www.readbyqxmd.com/read/28481873/restoring-pu-1-induces-apoptosis-and-modulates-viral-transactivation-via-interferon-stimulated-genes-in-primary-effusion-lymphoma
#13
H Goto, R Kariya, E Kudo, Y Okuno, K Ueda, H Katano, S Okada
Primary effusion lymphoma (PEL), which is an aggressive subgroup of B-cell lymphoma associated with Kaposi sarcoma-associated herpes virus/human herpes virus-8, is refractory to the standard treatment, and exhibits a poor survival. Although PU.1 is downregulated in PEL, the potential role of its reduction remains to be elucidated. In this investigation, we analyzed the DNA methylation of PU.1 cis-regulatory elements in PEL and the effect of restoring PU.1 on PEL cells. The mRNA level of PU.1 was downregulated in PEL cells...
May 8, 2017: Oncogene
https://www.readbyqxmd.com/read/28473904/from-chronic-immune-thrombocytopenia-to-severe-aplastic-anemia-recent-insights-into-the-evolution-of-eltrombopag
#14
REVIEW
Harinder Gill, Raymond S M Wong, Yok-Lam Kwong
Thrombopoietin (TPO) is the most potent cytokine stimulating thrombopoiesis. Therapy with exogenous TPO is limited by the formation of antibodies cross-reacting with endogenous TPO. Mimetics of TPO are compounds with no antigenic similarity to TPO. Eltrombopag is an orally-active nonpeptide small molecule that binds to the transmembrane portion of the TPO receptor MPL. Initial trials of eltrombopag have centered on immune thrombocytopenia (ITP), which is due to both increased destruction and decreased production of platelets...
May 2017: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/28473813/asunaprevir-evokes-hepatocytes-innate-immunity-to-restrict-the-replication-of-hepatitis-c-and-dengue-virus
#15
Wei-Lun Tsai, Jin-Shiung Cheng, Chih-Wen Shu, Kwok-Hung Lai, Hoi-Hung Chan, Chun-Ching Wu, Jing-Mei Wu, Ping-I Hsu, Raymond T Chung, Tsung-Hsien Chang
Type I Interferon-mediated innate immunity against Flaviviridae, such as Hepatitis C virus (HCV) and Dengue virus (DENV), involves TLR3, RIG-I-like receptor (RLR) and JAK-STAT signal pathways. Asunaprevir is a newly developed HCV protease inhibitor for HCV treatment. Whether, asunaprevir activates innate immunity to restrict viral infection is unclear. Thus, this study investigates the effect of asunaprevir on innate immunity and its influence on HCV and DENV infection. Huh 7.5.1, Hep-G2 cells, JFH-1 infection model, and DENV-2 infection were used for the analysis...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28468885/rubicon-modulates-antiviral-type-i-ifn-signaling-by-targeting-irf3-dimerization
#16
Jae-Hoon Kim, Tae-Hwan Kim, Hyun-Cheol Lee, Chamilani Nikapitiya, Md Bashir Uddin, Min-Eun Park, Eun Seo Lee, Kiramage Chathuranga, Thilina U B Herath, W A Gayan Chathuranga, Jong-Soo Lee
Rubicon is a part of a Beclin-1-Vps34-containing autophagy complex. Rubicon induces antimicrobial responses upon TLR stimulation, and functions as a feedback inhibitor to prevent unbalanced proinflammatory responses depending on dectin-1 signaling. However, the role played by Rubicon during antiviral immune responses, particularly the type I interferon responses remains largely unknown. Here, we report that Rubicon acts as a negative regulator for virus-triggered IFN signaling. Knockdown of Rubicon promoted type I interferon signaling and inhibited virus replication, while overexpression of Rubicon has the opposite effect...
May 3, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28468880/selective-activation-of-interferon-%C3%AE-signaling-by-zika-virus-ns5-protein
#17
Vidyanath Chaudhary, Kit-San Yuen, Jasper Fuk-Woo Chan, Ching-Ping Chan, Pei-Hui Wang, Jian-Piao Cai, Shuo Zhang, Mifang Liang, Kin-Hang Kok, Chi-Ping Chan, Kwok-Yung Yuen, Dong-Yan Jin
Severe complications of Zika virus (ZIKV) infection might be caused by inflammation. How ZIKV induces pro-inflammatory cytokines is not understood. In this study, we show opposite regulatory effect of ZIKV NS5 protein on interferon (IFN) signaling. Whereas ZIKV and its NS5 protein were potent suppressors of type I and type III IFN signaling, they were found to activate IFN-γ signaling. Inversely, IFN-γ augmented ZIKV replication. NS5 interacted with STAT2 and targeted it for ubiquitination and degradation, but had no influence on STAT1 stability or nuclear translocation...
May 3, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28467369/developmental-control-of-nramp1-slc11a1-expression-in-professional-phagocytes
#18
Mathieu F M Cellier
NRAMP1 (SLC11A1) is a professional phagocyte membrane importer of divalent metals that contributes to iron recycling at homeostasis and to nutritional immunity against infection. Analyses of data generated by several consortia and additional studies were integrated to hypothesize mechanisms restricting NRAMP1 expression to mature phagocytes. Results from various epigenetic and transcriptomic approaches were collected for mesodermal and hematopoietic cell types and compiled for combined analysis with results of genetic studies associating single nucleotide polymorphisms (SNPs) with variations in NRAMP1 expression (eQTLs)...
May 3, 2017: Biology
https://www.readbyqxmd.com/read/28459513/effects-and-mechanisms-of-bazhen-decoction-siwu-decoction-and-sijunzi-decoction-on-5-fluorouracil-induced-anemia-in-mice
#19
Yunan Tian, Yuke Xiang, Guoran Wan, Dong Wan, Huifeng Zhu, Tao Wang, Xian Yang
OBJECTIVE: To investigate the effects of Bazhen decoction (BZD), Siwu decoction (SWD) and Sijunzi decoction (SJZD) in mice with anemia induced by 5-fluorouracil (5-FU) and discussed the possible pharmacological hematopoietic mechanism to provide experimental evidence for the clinical use of the three classical prescriptions in the treatment of anemia. METHODS: Anemia was induced by intravenous injection of 5-FU and 80 female Kunming mice were randomly, assigned to oral administration of SWD, SJZD, or BZD daily for 10 days...
August 2016: Journal of Traditional Chinese Medicine, Chung i Tsa Chih Ying Wen Pan
https://www.readbyqxmd.com/read/28457491/chemoimmunotherapeutic-effect-of-combined-treatment-with-ex-vivo-generated-antigen-presenting-immune-cells-and-conventional-antitumor-agents-in-a-mouse-neuroblastoma-model
#20
Seiichiro Inoue, Yumiko Setoyama, Akio Odaka, Daiki Kitagawa, Yoshifumi Beck
PURPOSE: Combining antitumor immunotherapy with conventional intensive multimodal therapy may be considered for advanced neuroblastoma. We investigated combination therapy with ex vivo generated immunostimulatory cells and intraperitoneal doxorubicin. METHODS: Immunogenic death of neuro-2a neuroblastoma cells was induced by doxorubicin or cisplatin (negative control). Mouse bone marrow cells were cultured with granulocyte-macrophage colony-stimulating factor, followed by addition of doxorubicin-killed neuro-2a cells with or without interleukin-4 and/or CpG-oligodeoxynucleotide to induce immunostimulatory cells...
April 21, 2017: Journal of Pediatric Surgery
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