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Liang Wei, Qi Wang, Yanfei Zhang, Cheng Yang, Hongxin Guan, Jianxin Jiang, Zhiyang Sun
Intracranial aneurysm (IA) is a localized dilation of the blood vessel. The present study was designed to explore the mechanisms of rupture of IA. GSE13353 (including 11 ruptured and 8 unruptured IA samples) and GSE15629 (including 8 ruptured and 6 unruptured IA samples) were downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) identified using limma and MetaDE packages were merged, and a protein-protein interaction (PPI) network analysis was performed using Cytoscape software...
April 2018: Oncology Letters
Jihui Zhang, Jie Chen, Shannon C Mangat, Chathuri Perera Baruhupolage, David R Garrod, Clive Robinson
INTRODUCTION: Intracellular reactive oxidant species (ROS) are generated in human airway epithelial cells by the prothrombinase action of Group 1 house dust mite (HDM) allergens and by ligation of viral RNA sensor Toll-like receptors (TLRs). We explored signaling convergence between HDM allergens and TLRs in ROS generation because epithelial cells form the primary barrier against inhaled substances and dictate host responses to allergens and viruses. METHODS: ROS formation by Calu-3 human airway cells was studied by measuring dihydrorhodamine 123 oxidation after activation by polyinosinic:polycytidylic acid (to activate TLR3), CL097 (to activate TLR7), a natural mixture of HDM allergens, or BzATP...
March 15, 2018: Immunity, Inflammation and Disease
Mabrouka Salem, Alain Tremblay, Julie Pelletier, Bernard Robaye, Jean Sévigny
In this study, we investigated the role of extracellular nucleotides in chemokine (KC, MIP-2, MCP-1, and CXCL10) expression and secretion by murine primary intestinal epithelial cells (IECs) with a focus on P2Y6 receptors. qRT-PCR experiments showed that P2Y6 was the dominant nucleotide receptor expressed in mouse IEC. In addition, the P2Y6 ligand UDP induced expression and secretion of CXCL10. For the other studies, we took advantage of mice deficient in P2Y6 ( P2ry6 -/- ). Similar expression levels of P2Y1 , P2Y2 , P2X2, P2X4, and A2A were detected in P2ry6 -/- and WT IEC...
2018: Frontiers in Pharmacology
Motoya Murase, Takumi Kawasaki, Rika Hakozaki, Takuya Sueyoshi, Dyaningtyas Dewi Pamungkas Putri, Yuichi Kitai, Shintaro Sato, Masahito Ikawa, Taro Kawai
TLRs recognize pathogen components and drive innate immune responses. They localize at either the plasma membrane or intracellular vesicles such as endosomes and lysosomes, and proper cellular localization is important for their ligand recognition and initiation of signaling. In this study, we disrupted ATP6V0D2, a component of vacuolar-type H+ adenosine triphosphatase (V-ATPase) that plays a central role in acidification of intracellular vesicles, in a macrophage cell line. ATP6V0D2-deficient cells exhibited reduced cytokine production in response to endosome-localized, nucleic acid-sensing TLR3, TLR7, and TLR9, but enhanced inflammatory cytokine production and NF-κB activation following stimulation with LPS, a TLR4 agonist...
March 14, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
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
Megan A Schilling, Robab Katani, Sahar Memari, Meredith Cavanaugh, Joram Buza, Jessica Radzio-Basu, Fulgence N Mpenda, Melissa S Deist, Susan J Lamont, Vivek Kapur
Traditional approaches to assess the immune response of chickens to infection are through animal trials, which are expensive, require enhanced biosecurity, compromise welfare, and are frequently influenced by confounding variables. Since the chicken embryo becomes immunocompetent prior to hatch, we here characterized the transcriptional response of selected innate immune genes to Newcastle disease virus (NDV) infection in chicken embryos at days 10, 14, and 18 of embryonic development. The results suggest that the innate immune response 72 h after challenge of 18-day chicken embryo is both consistent and robust...
2018: Frontiers in Genetics
Oliver Grünvogel, Ombretta Colasanti, Ji-Young Lee, Volker Klöss, Sandrine Belouzard, Anna Reustle, Katharina Esser-Nobis, Jasper Hesebeck-Brinckmann, Pascal Mutz, Katrin Hoffmann, Arianeb Mehrabi, Ronald Koschny, Florian W R Vondran, Daniel Gotthardt, Paul Schnitzler, Christoph Neumann-Haefelin, Robert Thimme, Marco Binder, Ralf Bartenschlager, Jean Dubuisson, Alexander H Dalpke, Volker Lohmann
BACKGROUND & AIMS: Hepatitis C virus (HCV) infections most often result in chronic outcomes, although the virus constantly produces replication intermediates, in particular double-stranded RNA (dsRNA), representing potent inducers of innate immunity. We aimed to characterize the fate of HCV dsRNA in hepatocyte cultures to identify mechanisms contributing to viral persistence in presence of an active innate immune response. METHODS: We analyzed hepatocyte-based culture models for HCV for induction of innate immunity, secretion of virus positive- or negative-strand RNA, and viral replication using different quantification methods and microscopy techniques...
March 10, 2018: Gastroenterology
Hanaa Ahmed-Hassan, Mohamed Sarjoon Abdul-Cader, Upasama De Silva Senapathi, Maha Ahmed Sabry, Eman Hamza, Eva Nagy, Shayan Sharif, Mohamed Faizal Abdul-Careem
BACKGROUND: Toll like receptor (TLR) 3 is a critically important innate pattern recognizing receptor that senses many viral infections. Although, it has been shown that double stranded (ds) RNA can be used for the stimulation of TLR3 signaling pathway in a number of host-viral infection models, it's effectiveness as an antiviral agent against low pathogenic avian influenza virus (LPAIV) needs further investigation. METHODS: In this study, first, we delivered TLR3 ligand, dsRNA, in ovo at embryo day (ED)18 since in ovo route is routinely used for vaccination against poultry viral and parasitic infections and infected with H4N6 LPAIV 24-h post-treatment...
March 12, 2018: Virology Journal
Azza M EzzEl-Din, Sherif H Galal, Asmaa O Ahmed, Sherif I Kamel, Dalia T Kamal
Hepatitis B virus (HBV) is the one of the major causes of chronic liver disease. Individuals exposed to HBV show wide spectrum outcomes including immunized persons, asymptomatic carrier, chronic active hepatitis, cirrhosis and HCC. The outcome of HBV infection and the severity of associated liver diseases are determined by the nature and strength of host immune responses against the virus. There is accumulating evidence that the innate branch of the host immune system plays an important role in the control of HBV infection...
June 2017: Egyptian Journal of Immunology
Tsukasa Seya, Yohei Takeda, Ken Takashima, Sumito Yoshida, Masahiro Azuma, Misako Matsumoto
The immune system eliminates advanced cancer when treated with programmed cell death protein-1 (PD-1) or its ligand (PD-L1) blockade, but PD-1 therapy is effective in only ∼20% of patients with solid cancer. The PD-1 antibody mainly acts on the effector phase of cytotoxic T lymphocytes (CTLs) in tumors but induces no activation of the priming phase of antigen-presenting dendritic cells (DCs). It is reasonable that both DC-priming and PD-1/L1 blocking are mandatory for efficient CTL-mediated tumor cytolysis...
2018: Proceedings of the Japan Academy. Series B, Physical and Biological Sciences
Shanmao Cao, Lijie Zhu, Hongtao Nie, Minghao Yin, Gang Liu, Xiwu Yan
Crassadoma gigantea is an important commercial marine bivalve species in Baja California and Mexico. In this study, we have applied RNA-Seq technology to profile the transcriptome of the C. gigantea for the first time. A total of 80,832,518 raw reads were produced from a Illumina HiSeq4000 platform, and 77,306,198 (95.64%) clean reads were generated after trimming the adaptor sequences. The transcriptome assembled into 158,855 transcripts with an N50 size of 1995 bp and an average size of 1008 bp. A number of DNA repair related genes, such as MSH3, EGF, TGF, IGF, FGF, encoding different groups of growth factors were found in the transcriptome data of C...
March 7, 2018: Gene
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
Ah-Yeon Kim, Hyun-Jin Shim, Hyeon-Myeong Shin, Yoo Jung Lee, Hyeonjeong Nam, Su Yeon Kim, Hyung-Sun Youn
Toll-like receptors (TLRs) play a crucial role in danger recognition and induction of innate immune response against bacterial and viral infections. The TLR adaptor molecule, toll-interleukin-1 receptor domain-containing adapter inducing interferon-β (TRIF), facilitates TLR3 and TLR4 signaling, leading to the activation of the transcription factor, NF-κB and interferon regulatory factor 3 (IRF3). Andrographolide, the active component of Andrographis paniculata, exerts anti-inflammatory effects; however, the principal molecular mechanisms remain unclear...
March 1, 2018: International Immunopharmacology
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
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
Louise Ritchie, Rothwell Tate, Luke H Chamberlain, Graham Robertson, Michele Zagnoni, Teresa Sposito, Selina Wray, John A Wright, Clare E Bryant, Nicholas J Gay, Trevor J Bushell
Toll like receptor 3 (TLR3) belongs to a family of pattern recognition receptors that recognise molecules found on pathogens referred to as pathogen associated molecular patterns (PAMPs). Its involvement in innate immunity is well known but despite its presence in the central nervous system (CNS), our knowledge of its function is limited. Here, we have investigated whether TLR3 activation modulates synaptic activity in primary hippocampal cultures and induced pluripotent stem cell (iPSC)-derived neurons. Synaptically driven spontaneous action potential (AP) firing was significantly reduced by the TLR3 specific activator, poly I:C, in a concentration-dependent manner following both short (5 min) and long exposures (1h) in rat hippocampal cultures...
March 2, 2018: Neuropharmacology
Mary-Anne Hartley, Remzi O Eren, Matteo Rossi, Florence Prevel, Patrik Castiglioni, Nathalie Isorce, Chantal Desponds, Lon-Fye Lye, Stephen M Beverley, Stefan K Drexler, Nicolas Fasel
The various symptomatic outcomes of cutaneous leishmaniasis relates to the type and potency of its underlying inflammatory responses. Presence of the cytoplasmic Leishmania RNA virus-1 (LRV1) within Leishmania guyanensis , worsens lesional inflammation and parasite burden, as the viral dsRNA genome acts as a potent innate immunogen stimulating Toll-Like-Receptor-3 (TLR3). Here we investigated other innate pattern recognition receptors capable of reacting to dsRNA and potentially contributing to LRV1-mediated inflammatory pathology...
January 14, 2018: Microbial Cell
Y Y Zhu, Q Li, Y M Zhang, Y H Zhou
OBJECTIVE: To investigate the effects of Toll like receptors on the osteogenesis of human pe-riodontal ligament stem cells (hPDLSCs) and probable molecular mechanism. METHODS: Real-time PCR and flow cytometry were applied to test the expression of TLRs in hPDLSCs and the positive cell percentage of TLR. hPDLSCs were cultured in osteogenic medium for 7 to 14 days with different TLR agonists at various concentrations . The effect of different TLR on osteogenic differentiation of hPDLSCs was evaluated by alizarin red S staining, alkaline phosphatase (ALP) staining and ALP activity assay...
February 18, 2018: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
Yan-Hong Yong, Shao-Feng Liu, Guo-Hong Hua, Ru-Min Jia, Ravi Gooneratne, Yun-Tao Zhao, Ming Liao, Xiang-Hong Ju
Induction of the innate immune pathways is critical for early anti-viral defense. How geese recognize viral molecules and activate these pathways is not well understood. In mammals, Toll-like receptor 3 (TLR3) recognizes double-stranded RNA. Activation of TLR3 induces the activation of NF-кB and the production of type-I interferon. In this study, the goose TLR3 gene was cloned using rapid amplification of cDNA ends. Goose TLR3 encoded an 896-amino-acid protein, containing a signal secretion peptide, 14 extracellular leucine-rich repeat domains, a transmembrane domain, a Toll/interleukin-1 receptor signaling domain, and shared 46...
March 2018: Veterinary Immunology and Immunopathology
Ryo Okada, Xinwen Zhang, Yuka Harada, Zhou Wu, Hiroshi Nakanishi
OBJECTIVE: The objective of this study is to investigate the role of cathepsin H (CatH), a lysosomal cysteine protease, in the development of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. METHODS: EAE was induced in CatH-deficient mice (CatH-/- ) and wild-type littermates (+/+) using myelin oligodendrocyte glycoprotein (MOG) 35-55. The effects of CatH deficiency were determined by clinical scoring, mRNA expression levels of Tbx21, Rorc and FoxP3, protein levels of poly(I:C)-induced toll-like receptor 3 (TLR3) and phosphorylation of IRF3, and secretion of interferon-β (IFN-β) by splenocytes...
February 22, 2018: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
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