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Interferon regulatory factor

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https://www.readbyqxmd.com/read/28422760/cannabinoid-cb1-receptor-overactivity-contributes-to-the-pathogenesis-of-idiopathic-pulmonary-fibrosis
#1
Resat Cinar, Bernadette R Gochuico, Malliga R Iyer, Tony Jourdan, Tadafumi Yokoyama, Joshua K Park, Nathan J Coffey, Hadass Pri-Chen, Gergő Szanda, Ziyi Liu, Ken Mackie, William A Gahl, George Kunos
Idiopathic pulmonary fibrosis (IPF) is a life-threatening disease without effective treatment, highlighting the need for identifying new targets and treatment modalities. The pathogenesis of IPF is complex, and engaging multiple targets simultaneously might improve therapeutic efficacy. To assess the role of the endocannabinoid/cannabinoid receptor 1 (endocannabinoid/CB1R) system in IPF and its interaction with inducible nitric oxide synthase (iNOS) as dual therapeutic targets, we analyzed lung fibrosis and the status of the endocannabinoid/CB1R system and iNOS in mice with bleomycin-induced pulmonary fibrosis (PF) and in lung tissue and bronchoalveolar lavage fluid (BALF) from patients with IPF, as well as controls...
April 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28419615/involvement-of-herpes-simplex-virus-type-1-ul13-protein-kinase-in-the-induction-of-socs-genes-the-negative-regulator-of-cytokine-signaling
#2
Yuka Sato, Tetsuo Koshizuka, Kei Ishibashi, Koichi Hashimoto, Ken Ishioka, Kazufumi Ikuta, Shin-Ichi Yokota, Nobuhiro Fujii, Tatsuo Suzutani
The suppressor of cytokine signaling (SOCS) family consists of 8 members and suppresses various cytokine signaling pathways including interferon (IFN) signaling. Therefore, some viruses have evolved molecular mechanisms to induce SOCS proteins in order to escape from host immunity. Herpes simplex virus type 1 (HSV-1) has a mechanism for escaping from type I IFN by induction of SOCS1 and SOCS3 as well. In this study, expression of 8 members of the SOCS family by HSV-1 infection was comparatively analyzed by quantitative reverse transcription PCR...
April 17, 2017: Microbiology and Immunology
https://www.readbyqxmd.com/read/28413316/ginsenoside-rc-from-panax-ginseng-exerts-anti-inflammatory-activity-by-targeting-tank-binding-kinase-1-interferon-regulatory-factor-3-and-p38-atf-2
#3
Tao Yu, Yanyan Yang, Yi-Seong Kwak, Gwan Gyu Song, Mi-Yeon Kim, Man Hee Rhee, Jae Youl Cho
BACKGROUND: Ginsenoside Rc (G-Rc) is one of the major protopanaxadiol-type saponins isolated from Panax ginseng, a well-known medicinal herb with many beneficial properties including anticancer, anti-inflammatory, antiobesity, and antidiabetic effects. In this study, we investigated the effects of G-Rc on inflammatory responses in vitro and examined the mechanisms of these effects. METHODS: The in vitro inflammation system used lipopolysaccharide-treated macrophages, tumor necrosis factor-α/interferon-γ-treated synovial cells, and HEK293 cells transfected with various inducers of inflammation...
April 2017: Journal of Ginseng Research
https://www.readbyqxmd.com/read/28413195/purinergic-signaling-in-microglia-in-the-pathogenesis-of-neuropathic-pain
#4
Kazuhide Inoue
Nerve injury often causes debilitating chronic pain, referred to as neuropathic pain, which is refractory to currently available analgesics including morphine. Many reports indicate that activated spinal microglia evoke neuropathic pain. The P2X4 receptor (P2X4R), a subtype of ionotropic ATP receptors, is upregulated in spinal microglia after nerve injury by several factors, including CC chemokine receptor CCR2, the extracellular matrix protein fibronectin in the spinal cord, interferon regulatory factor 8 (IRF8) and IRF5...
2017: Proceedings of the Japan Academy. Series B, Physical and Biological Sciences
https://www.readbyqxmd.com/read/28409399/pro-apoptotic-signaling-induced-by-retinoic-acid-and-dsrna-is-under-the-control-of-interferon-regulatory-factor-3-in-breast-cancer-cells
#5
Ana R Bernardo, José M Cosgaya, Ana Aranda, Ana M Jiménez-Lara
Breast cancer is one of the most lethal malignancies for women. Retinoic acid (RA) and double-stranded RNA (dsRNA) are considered signaling molecules with potential anticancer activity. RA, co-administered with the dsRNA mimic polyinosinic-polycytidylic acid (poly(I:C)), synergizes to induce a TRAIL (Tumor-Necrosis-Factor Related Apoptosis-Inducing Ligand)- dependent apoptotic program in breast cancer cells. Here, we report that RA/poly(I:C) co-treatment, synergically, induce the activation of Interferon Regulatory Factor-3 (IRF3) in breast cancer cells...
April 13, 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28408438/prdm16-represses-the-type-i-interferon-response-in-adipocytes-to-promote-mitochondrial-and-thermogenic-programing
#6
Megan Kissig, Jeff Ishibashi, Matthew J Harms, Hee-Woong Lim, Rachel R Stine, Kyoung-Jae Won, Patrick Seale
Brown adipose has the potential to counteract obesity, and thus, identifying signaling pathways that regulate the activity of this tissue is of great clinical interest. PRDM16 is a transcription factor that activates brown fat-specific genes while repressing white fat and muscle-specific genes in adipocytes. Whether PRDM16 also controls other gene programs to regulate adipocyte function was unclear. Here, we identify a novel role for PRDM16 in suppressing type I interferon (IFN)-stimulated genes (ISGs), including Stat1, in adipocytes in vitro and in vivo Ectopic activation of type I IFN signaling in brown adipocytes induces mitochondrial dysfunction and reduces uncoupling protein 1 (UCP1) expression...
April 13, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28404737/reprogramming-interferon-regulatory-factor-signaling-in-cardiometabolic-diseases
#7
REVIEW
Yaxing Zhang, Hongliang Li
Interferon regulatory factors (IRFs) are evolutionarily conserved proteins expressed not only in immune cells but also in other tissues and organs outside the immune system. In this review, we discuss mechanisms responsible for IRF-mediated innate immune responses and the function and mechanism of IRFs in cardiometabolic diseases. We focus on the role of IRFs in innate immunity and cardiometabolic homeostasis, and highlight reprogrammed IRF signaling.
May 2017: Physiology
https://www.readbyqxmd.com/read/28399967/type-1-polarised-dendritic-cells-are-a-potent-immunogen-against-mycobacterium-tuberculosis
#8
Y Satake, Y Nakamura, M Kono, H Hozumi, T Nagata, K Tsujimura, N Enomoto, T Fujisawa, N Inui, T Fujiyama, Y Tokura, T Matsui, K Yokomura, M Shirai, H Hayakawa, T Suda
OBJECTIVE: Application of immunotherapy using dendritic cells (DCs) is considered an effective treatment strategy against persistent Mycobacterium tuberculosis infection. With the goal of developing improved therapeutic vaccination strategies for patients with tuberculosis (TB), we tested the ability of ex vivo-generated DCs to induce an effective TB antigen-specific type-1 immune response. METHODS: Monocyte-derived DCs from TB patients were induced to mature using a 'standard' cytokine cocktail (interleukin [IL] 1β, tumour necrosis factor alpha [TNF-α], IL-6 and prostaglandin E2) or a type 1-polarised DC (DC1) cocktail (IL-1β, TNF-α, interferon [IFN] α, IFN-γ and polyinosinic:polycytidylic acid), and were loaded with the established TB antigen 6-kDa early secretory antigenic target protein (ESAT-6)...
May 1, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/28399655/cyclic-gmp-amp-as-an-endogenous-second-messenger-in-innate-immune-signaling-by-cytosolic-dna
#9
Kazuki Kato, Hiroki Omura, Ryuichiro Ishitani, Osamu Nureki
The innate immune system functions as the first line of defense against invading bacteria and viruses. In this context, the cGAS/STING [cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase/ STING] signaling axis perceives the nonself DNA associated with bacterial and viral infections, as well as the leakage of self DNA by cellular dysfunction and stresses, to elicit the host's immune responses. In this pathway, the noncanonical cyclic dinucleotide 2',3'-cyclicGMP-AMP(2',3'-cGAMP) functions as a second messenger for signal transduction: 2',3'-cGAMP is produced by the enzyme cGAS upon its recognition of double-stranded DNA, and then the 2',3'-cGAMP is recognized by the receptor STING to induce the phosphorylation of downstream factors, including TBK1 (TANK binding kinase 1) and IRF3 (interferon regulatory factor 3)...
April 7, 2017: Annual Review of Biochemistry
https://www.readbyqxmd.com/read/28399143/sphingosine-1-phosphate-receptor-1-s1pr1-agonist-cym5442-inhibits-expression-of-intracellular-adhesion-molecule-1-icam1-in-endothelial-cells-infected-with-influenza-a-viruses
#10
Hao Jiang, Si-Mei Shen, Jie Yin, Peng-Peng Zhang, Yi Shi
BACKGROUND: Influenza A virus infection and its complications effect a large population worldwide. Endothelial cells are an important component in lung inflammation caused by influenza A virus infection. The roles of endothelial sphingosine 1-phophate receptor 1 (S1PR1) in the regulation of molecules involved in leukocyte recruitment during influenza A virus infection still remain unknown. In this report, we tested our hypothesis that S1PR1 agonist CYM5442 inhibits expression of intracellular adhesion molecules 1 (ICAM1) in endothelial cells infected with influenza A virus...
2017: PloS One
https://www.readbyqxmd.com/read/28398870/interleukin-35-rescues-regulatory-b-cell-function-but-the-effect-is-dysregulated-in-ulcerative-colitis
#11
Shaoxuan Wang, Chengyong Qin
Ulcerative colitis (UC) is a long-time inflammatory condition arising from aberrant immune activation in the colon and the rectum. Interleukin (IL)-35 plays critical roles in autoimmune disorders. In this study, we explored the pathways of IL-35 in affecting UC. First, peripheral blood mononuclear cells (PBMCs) from UC patients were obtained. Pretreating PBMCs with IL-35 resulted in significantly elevated IL-10 production from whole PBMCs as well as B cells, whereas pretreating PBMCs with IL-12 or IL-27 did not demonstrate a similar effect...
February 16, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28398673/melatonin-alleviates-inflammasome-induced-pyroptosis-through-inhibiting-nf-%C3%AE%C2%BAb-gsdmd-signal-in-mice-adipose-tissue
#12
Zhenjiang Liu, Lu Gan, Yatao Xu, Dan Luo, Qian Ren, Song Wu, Chao Sun
Pyroptosis is a proinflammatory form of cell death that is associated with pathogenesis of many chronic inflammatory diseases. Melatonin is substantially reported to possess anti-inflammatory properties by inhibiting inflammasome activation. However, the effects of melatonin on inflammasome-induced pyroptosis in adipocytes remain elusive. Here, we demonstrated that melatonin alleviated lipopolysaccharides (LPS)-induced inflammation and NLRP3 inflammasome formation in mice adipose tissue. The NLRP3 inflammasome-mediated pyroptosis was also inhibited by melatonin in adipocytes...
April 11, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28398495/a-histological-study-of-fulminant-type-1-diabetes-mellitus-related-to-human-cytomegalovirus-reactivation
#13
Sho Yoneda, Akihisa Imagawa, Kenji Fukui, Sae Uno, Junji Kozawa, Makoto Sakai, Toshiki Yumioka, Hiromi Iwahashi, Iichiro Shimomura
Context: Fulminant type 1 diabetes mellitus (T1DM) is thought to be partly caused by virus infection. Objective: This study investigated the mechanism of β cell destruction in fulminant T1DM after drug-induced hypersensitivity syndrome (DIHS). Methods: We determined the localization of viruses of human cytomegalovirus (HCMV), human herpesvirus 6 (HHV-6) and Epstein-Barr virus (EBV), and the expression of interferon regulatory factor 3 (IRF3) and viral receptors of Z DNA binding protein 1 (ZBP1) and retinoic acid-inducible gene I (RIG-I), together with inflammatory cells by immunohistochemistry of pancreas from an autopsy fulminant T1DM patient with DIHS or seven subjects with normal glucose tolerance who underwent pancreatectomy...
April 10, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28396748/innate-immune-responses-induced-by-lipopolysaccharide-and-lipoteichoic-acid-in-primary-goat-mammary-epithelial-cells
#14
Omar Bulgari, Xianwen Dong, Alfred L Roca, Anna M Caroli, Juan J Loor
BACKGROUND: Innate immune responses induced by in vitro stimulation of primary mammary epithelial cells (MEC) using Gram-negative lipopolysaccharide (LPS) and Gram-positive lipoteichoic acid (LTA) bacterial cell wall components are well- characterized in bovine species. The objective of the current study was to characterize the downstream regulation of the inflammatory response induced by Toll-like receptors in primary goat MEC (pgMEC). We performed quantitative real-time RT-PCR (qPCR) to measure mRNA levels of 9 genes involved in transcriptional regulation or antibacterial activity: Toll-like receptor 2 (TLR2), Toll-like receptor 4 (TLR4), prostaglandin-endoperoxide synthase 2 (PTGS2), interferon induced protein with tetratricopeptide repeats 3 (IFIT3), interferon regulatory factor 3 (IRF3), myeloid differentiation primary response 88 (MYD88), nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (NFKB1), Toll interacting protein (TOLLIP), and lactoferrin (LTF)...
2017: Journal of Animal Science and Biotechnology
https://www.readbyqxmd.com/read/28396670/grass-carp-laboratory-of-genetics-and-physiology-2-serves-as-a-negative-regulator-in-retinoic-acid-inducible-gene-i-and-melanoma-differentiation-associated-gene-5-mediated-antiviral-signaling-in-resting-state-and-early-stage-of-grass-carp-reovirus-infection
#15
Youliang Rao, Quanyuan Wan, Chunrong Yang, Jianguo Su
Laboratory of genetics and physiology 2 (LGP2) is a key component of RIG-I-like receptors (RLRs). However, the lack of the caspase recruitment domains (CARDs) results in its controversial functional performance as a negative or positive regulator in antiviral responses. Especially, no sufficient evidence uncovers the functional mechanisms of LGP2 in RLR signaling pathways in teleost. Here, negative regulation mechanism of LGP2 in certain situations in retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5)-mediated antiviral responses was identified in Ctenopharyngodon idella kidney cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28388578/the-tumor-suppressor-interferon-regulatory-factor-8-inhibits-%C3%AE-catenin-signaling-in-breast-cancers-but-is-frequently-silenced-by-promoter-methylation
#16
Xinrong Luo, Xin Xiong, Qing Shao, Tingxiu Xiang, Lili Li, Xuedong Yin, Xia Li, Qian Tao, Guosheng Ren
Interferon (IFN) regulatory factor 8 is encoded by a novel candidate tumor suppressor gene (IRF8), its promotor is frequently methylated in multiple cancers. However, the promoter methylation status, functions and underlying mechanisms of IRF8 in breast cancer remain unclear. We found that IRF8 was downregulated in breast cancer cell lines and primary tumors, compared with normal breast tissues, mainly because of aberrant promoter methylation. However, its expression was not associated with pathological characteristics...
March 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28386100/petri-net-computational-modelling-of-langerhans-cell-interferon-regulatory-factor-network-predicts-their-role-in-t-cell-activation
#17
Marta E Polak, Chuin Ying Ung, Joanna Masapust, Tom C Freeman, Michael R Ardern-Jones
Langerhans cells (LCs) are able to orchestrate adaptive immune responses in the skin by interpreting the microenvironmental context in which they encounter foreign substances, but the regulatory basis for this has not been established. Utilising systems immunology approaches combining in silico modelling of a reconstructed gene regulatory network (GRN) with in vitro validation of the predictions, we sought to determine the mechanisms of regulation of immune responses in human primary LCs. The key role of Interferon regulatory factors (IRFs) as controllers of the human Langerhans cell response to epidermal cytokines was revealed by whole transcriptome analysis...
April 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28386004/reovirus-infection-triggers-inflammatory-responses-to-dietary-antigens-and-development-of-celiac-disease
#18
Romain Bouziat, Reinhard Hinterleitner, Judy J Brown, Jennifer E Stencel-Baerenwald, Mine Ikizler, Toufic Mayassi, Marlies Meisel, Sangman M Kim, Valentina Discepolo, Andrea J Pruijssers, Jordan D Ernest, Jason A Iskarpatyoti, Léa M M Costes, Ian Lawrence, Brad A Palanski, Mukund Varma, Matthew A Zurenski, Solomiia Khomandiak, Nicole McAllister, Pavithra Aravamudhan, Karl W Boehme, Fengling Hu, Janneke N Samsom, Hans-Christian Reinecker, Sonia S Kupfer, Stefano Guandalini, Carol E Semrad, Valérie Abadie, Chaitan Khosla, Luis B Barreiro, Ramnik J Xavier, Aylwin Ng, Terence S Dermody, Bana Jabri
Viral infections have been proposed to elicit pathological processes leading to the initiation of T helper 1 (TH1) immunity against dietary gluten and celiac disease (CeD). To test this hypothesis and gain insights into mechanisms underlying virus-induced loss of tolerance to dietary antigens, we developed a viral infection model that makes use of two reovirus strains that infect the intestine but differ in their immunopathological outcomes. Reovirus is an avirulent pathogen that elicits protective immunity, but we discovered that it can nonetheless disrupt intestinal immune homeostasis at inductive and effector sites of oral tolerance by suppressing peripheral regulatory T cell (pTreg) conversion and promoting TH1 immunity to dietary antigen...
April 7, 2017: Science
https://www.readbyqxmd.com/read/28380480/hemodialysis-patients-display-a-declined-proportion-of-th2-and-regulatory-t-cells-in-parallel-with-a-high-interferon-%C3%AE-profile
#19
Ladan Mansouri, Anna Nopp, Stefan H Jacobson, Britta Hylander, Joachim Lundahl
BACKGROUND: A high prevalence of cardiovascular diseases (CVDs) and infections in patients with chronic kidney disease (CKD) arises partly due to a high inflammatory state and aberrations in immune cells function. Following in vitro stimulation of leukocytes with different T-cell mitogens, we observed a lower level of interleukin (IL)-2 and IL-10 production in CKD patients. To gain more knowledge as to whether this is the result of an alteration in T-cell function, we investigated the T-cell subsets profile and cytokine production in hemodialysis patients...
April 6, 2017: Nephron
https://www.readbyqxmd.com/read/28369997/gene-expression-profile-after-knockdown-of-usp18-in-hepg2-2-15-cells
#20
Lin Li, Qing-Song Lei, Ling-Na Kong, Shu-Jun Zhang, Bo Qin
In our previous work, we found that the expression of ubiquitin-specific protease 18 (USP18), also known as UBP43, is associated with the efficiency of interferon alpha (IFN-α) treatment in patients with chronic hepatitis B (CHB). To elucidate the influence of USP18 on hepatitis B virus (HBV) replication and the mechanism of this activity, we silenced USP18 by introducing short hairpin RNA (shRNA) into Hepg2.2.15 cells. To identify the changed genes and pathways in Hepg2.2.15-shRNA-USP18 cells, we performed a microarray gene expression analysis to compare the Hepg2...
March 31, 2017: Journal of Medical Virology
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