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IFN-gamma signaling

Yang Tan, Xingxin Wu, Jing Sun, Wenjie Guo, Fangyuan Gong, Fenli Shao, Tao Tan, Yi Cao, Bingfeng Zheng, Yanhong Gu, Yang Sun, Qiang Xu
Interferon gamma (IFN-γ) signaling in T cells plays an important role in developing T helper 1 (Th1)-mediated inflammation. Selective regulation of IFN-γ signaling is an attractive strategy for treating Th1-mediated immune diseases. In this study, we aimed to explore possible means of targeting IFN-γ signaling by using small molecule compound. A synthetic small molecule FC9 was identified as it selectively inhibited IFN-γ signaling in T cells without suppressing interleukin 4 (IL-4) signaling. Furthermore, FC9 inhibited IFN-γ-induced Janus kinase 2 (JAK2) activation via competing with IFN-γ for binding to IFN-γ receptor 1 (IFN-γ R1)...
October 14, 2016: Biochemical Pharmacology
John Fenimore, Howard A Young
Interferon gamma, referred to here as IFN-γ, is a major component in immunological cell signaling and is a critical regulatory protein for overall immune system function. First discovered in 1965 (Wheelock Science 149: (3681)310-311, 1965), IFN-γ is the only Type II interferon identified. Its expression is both positively and negatively controlled by different factors. In this chapter, we will review the transcriptional and post-transcriptional control of IFN-γ expression. In the transcriptional control part, the regular activators and suppressors are summarized, we will also focus on the epigenetic control, such as chromosome access, DNA methylation, and histone acetylation...
2016: Advances in Experimental Medicine and Biology
R Krishnan Kutty, William Samuel, Kaifa Boyce, Aswini Cherukuri, Todd Duncan, Cynthia Jaworski, Chandrasekharam N Nagineni, T Michael Redmond
PURPOSE: Proinflammatory cytokines interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), and interleukin-1 beta (IL-1β) secreted by infiltrating lymphocytes or macrophages may play a role in triggering RPE dysfunction associated with age-related macular degeneration (AMD). Binding of these proinflammatory cytokines to their specific receptors residing on the RPE cell surface can activate signaling pathways that, in turn, may dysregulate cellular gene expression. The purpose of the present study was to investigate whether IFN-γ, TNF-α, and IL-1β have an adverse effect on the expression of genes essential for RPE function, employing the RPE cell line ARPE-19 as a model system...
2016: Molecular Vision
Diane E Griffin, Victoria K Baxter
Infection of mice with Sindbis virus (SINV) produces encephalomyelitis and provides a model for examination of the central nervous system (CNS) immune response to alphavirus infection. Clearance of infectious virus is accomplished through a cooperative effort between SINV-specific antibody and interferon gamma (IFN-γ), but the regulatory interactions are poorly understood. To determine the effects of IFN-γ on clinical disease and the antiviral immune response, C57BL/6 mice lacking IFN-γ (Ifng-/-) or IFN-γ receptor (Ifngr1-/-) were studied in comparison to wild-type (WT) mice...
September 22, 2016: Journal of General Virology
Jeremy W Duncan, Shakevia Johnson, Xiao Zhang, Baoying Zheng, Jia Luo, Xiao-Ming Ou, Craig A Stockmeier, Jun Ming Wang
BACKGROUND: Ethanol (EtOH) neurotoxicity can result in devastating effects on brain and behavior by disrupting homeostatic signaling cascades and inducing cell death. One such mechanism involves double-stranded RNA activated protein kinase (PKR), a primary regulator of protein translation and cell viability in the presence of a virus or other external stimuli. EtOH-mediated up-regulation of interferon-gamma (IFN-γ; the oxidative stress-inducible regulator of PKR), PKR, and its target, p53, are still being fully elucidated...
September 20, 2016: Alcoholism, Clinical and Experimental Research
Susanne Kleiderman, Simon Gutbier, Kemal Ugur Tufekci, Felipe Ortega, João V Sá, Ana P Teixeira, Catarina Brito, Enrico Glaab, Benedikt Berninger, Paula M Alves, Marcel Leist
Conversion of astrocytes to neurons, via de-differentiation to neural stem cells (NSC), may be a new approach to treat neurodegenerative diseases and brain injuries. The signaling factors affecting such a cell conversion are poorly understood, and they are hard to identify in complex disease models or conventional cell cultures. To address this question, we developed a serum-free, strictly controlled culture system of pure and homogeneous 'astrocytes generated form murine embryonic stem cells (ESC)'. These stem cell derived astrocytes (mAGES), as well as standard primary astrocytes resumed proliferation upon addition of FGF...
September 7, 2016: Stem Cells
Aikaterini Thanou, Stavros Stavrakis, John W Dyer, Melissa E Munroe, Judith A James, Joan T Merrill
BACKGROUND: Decreased heart rate variability (HRV) is associated with adverse outcomes in cardiovascular diseases and has been observed in patients with systemic lupus erythematosus (SLE). We examined the relationship of HRV with SLE disease activity and selected cytokine pathways. METHODS: Fifty-three patients from the Oklahoma Lupus Cohort were evaluated at two visits each. Clinical assessments included the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), British Isles Lupus Assessment Group (BILAG) index, physician global assessment (PGA), and Safety of Estrogens in Lupus Erythematosus National Assessment-SLEDAI Flare Index...
2016: Arthritis Research & Therapy
Hongyu Ren, Yuhong Li, Han Jiang, Minquan Du
INTRODUCTION: Preterm birth is a major cause for infant mortality and morbidity. A large number of studies have suggested a link between periodontal disease and preterm birth. The purpose of this study was to investigate the interaction between a periodontopathic bacterium Porphyromonas gingivalis and human extravillous trophoblast derived HTR8/SVneo cells. METHODS: Production of cytokines in HTR8 cells was measured via ELISA. Annexin V/PI flow cytometry was performed to assess apoptosis...
September 2016: Placenta
Eunyoung Lee, Sarah Chamanara, David Pleasure, Athena M Soulika
No abstract text is available yet for this article.
2016: Journal of Neuroinflammation
Jia Zhou, Jingjing Ling, Yong Wang, Jing Shang, Fengfeng Ping
Skin is the largest organ in our body and strategically placed to provide a metabolically active biological barrier against a range of noxious stressors. A lot of inflammatory cytokines, which are increased after ultraviolet (UV) irradiation produced by keratinocytes or other immunocytes, are closely related to pigmentary changes, including interleukin-18 (IL-18) and interferon-γ (IFN-γ). In this study, the effect of cross-talk between IL-18 and IFN-γ on melanogenesis was investigated. Treatment with IL-18 resulted in a dose-dependent increase of melanogenesis, while IFN-γ made an opposite effect...
October 2016: Journal of Photochemistry and Photobiology. B, Biology
Sunita Timalsena, Panwadee Pluangnooch, Adisak Wongkajornsilp, Kitipong Soontrapa
OBJECTIVE: Cytokine induced killer (CIK) cells are ex-vivo expanded T cells endowed with both T and Natural Killer cell properties. The standard protocol for generation of CIK cells is to culture peripheral blood mononuclear cells (PBMC) in the presence of interferon-gamma (IFN-γ), monoclonal antibody (mAb) against CD3 and interleukin-2 (IL-2). However, this protocol lacks costimulatory signal (CD28), crucial for T cell activation. Herein, the proliferation and functional properties of murine thymocytes derived CIK cells generated with or without costimulatory activation provided by anti-CD28 mAb were examined...
August 16, 2016: Asian Pacific Journal of Allergy and Immunology
C T Ng, L Y Fong, Y Y Low, J Ban, M N Hakim, Z Ahmad
The endothelial barrier function is tightly controlled by a broad range of signaling cascades including nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway. It has been proposed that disturbances in NO and cGMP production could interfere with proper endothelial barrier function. In this study, we assessed the effect of interferon-gamma (IFN-gamma), a pro-inflammatory cytokine, on NO and cGMP levels and examined the mechanisms by which NO and cGMP regulate the IFN-gamma-mediated HUVECs hyperpermeability...
August 19, 2016: Physiological Research
Ping Yu, Lijia Xiao, Lin Lin, Lingli Tang, Chunjing Chen, Fuyan Wang, Yong Wang
Inflammatory pathological injury caused by Chlamydia trachomatis persistent infection could lead to a variety of urogenital tract diseases. By comparing the cytokine production and PRR (pattern recognition receptor) expression between cell models with acute or persistent C. trachomatis infection, our data supported that persistent infection of C. trachomatis led to abnormal activation of toll-like receptor (TLR)2/4 signaling pathway and elevated IL-1α and IL-6 production, which was mediated by signal transducer and activator of transcription3 (STAT3)...
August 2016: Pathogens and Disease
Noriyuki Kaji, Kazuhide Horiguchi, Satoshi Iino, Shinsuke Nakayama, Tomohiko Ohwada, Yuko Otani, Firman, Takahisa Murata, Kenton M Sanders, Hiroshi Ozaki, Masatoshi Hori
The pacemaker function of interstitial cells of Cajal (ICC) is impaired during intestinal inflammation. The aim of this study is to clarify the pathophysiological mechanisms of ICC dysfunction during inflammatory condition by using intestinal cell clusters. Cell clusters were prepared from smooth muscle layer of murine jejunum and treated with interferon-gamma and lipopolysaccharide (IFN-γ+LPS) for 24h to induce inflammation. Pacemaker function of ICC was monitored by measuring cytosolic Ca(2+) oscillation in the presence of nifedipine...
September 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Pei-I Tsai, Adam Shih-Yuan Lee, Shu-Sheng Lee, Ming-Han Chung, Meng-Wei Liu, Chih-Kung Lee
For rapid screening and quantification of an antisera antibody, a nanometer bithiophene-based conductive biolinker can enhanced signal performance and can be used to verify the interaction of an anti-IFN-γ antibody with an IFN-γ protein. The experimental measurements take a generic approach which takes advantage of the functionality of thiophene-based linkers for biosensors. Effects associated with using bithiophene as a biolinker for surface plasmon resonance (SPR) spectroscopy are examined in this paper...
2016: PloS One
Fazlin Mohd Fauzi, Cini Mathew John, Arunkumar Karunanidhi, Hamse Y Mussa, Rajesh Ramasamy, Aishah Adam, Andreas Bender
ETHNOPHARMACOLOGICAL RELEVANCE: Cassia auriculata (CA) is used as an antidiabetic therapy in Ayurvedic and Siddha practice. This study aimed to understand the mode-of-action of CA via combined cheminformatics and in vivo biological analysis. In particular, the effect of 10 polyphenolic constituents of CA in modulating insulin and immunoprotective pathways were studied. MATERIALS AND METHODS: In silico target prediction was first employed to predict the probability of the polyphenols interacting with key protein targets related to insulin signalling, based on a model trained on known bioactivity data and chemical similarity considerations...
July 21, 2016: Journal of Ethnopharmacology
Priscila S Souza, Elaine D Gonçalves, Giulia S Pedroso, Hemelin R Farias, Stella C Junqueira, Rodrigo Marcon, Talita Tuon, Maíra Cola, Paulo C L Silveira, Adair R Santos, João B Calixto, Cláudio T Souza, Ricardo A de Pinho, Rafael C Dutra
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) caused by demyelination, immune cell infiltration, and axonal damage. Herein, we sought to investigate the influence of physical exercise on mice experimental autoimmune encephalomyelitis (EAE), a reported MS model. Data show that both strength and endurance training protocols consistently prevented clinical signs of EAE and decreased oxidative stress, an effect which was likely due to improving genomic antioxidant defense-nuclear factor erythroid 2-related factor (Nrf2)/antioxidant response elements (ARE) pathway-in the CNS...
July 22, 2016: Molecular Neurobiology
Barbara A Fox, Kiah L Sanders, Leah M Rommereim, Rebekah B Guevara, David J Bzik
Nonreplicating type I uracil auxotrophic mutants of Toxoplasma gondii possess a potent ability to activate therapeutic immunity to established solid tumors by reversing immune suppression in the tumor microenvironment. Here we engineered targeted deletions of parasite secreted effector proteins using a genetically tractable Δku80 vaccine strain to show that the secretion of specific rhoptry (ROP) and dense granule (GRA) proteins by uracil auxotrophic mutants of T. gondii in conjunction with host cell invasion activates antitumor immunity through host responses involving CD8α+ dendritic cells, the IL-12/interferon-gamma (IFN-γ) TH1 axis, as well as CD4+ and CD8+ T cells...
July 2016: PLoS Genetics
Rui Yamaguchi, Takatoshi Yamamoto, Arisa Sakamoto, Yasuji Ishimaru, Shinji Narahara, Hiroyuki Sugiuchi, Yasuo Yamaguchi
Interferon (IFN)-gamma is highly expressed in atherosclerotic lesions and may have an important role in atherogenesis. Myeloperoxidase (MPO), the most abundant protein in neutrophils, is a marker of plaque vulnerability and a possible bridge between inflammation and cardiovascular disease. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has also been implicated in the pathogenesis of atherosclerosis. The present study investigated the role of neutrophil activation in atherosclerosis. Adherent macrophages were obtained from primary cultures of human mononuclear cells...
February 2016: Heliyon
Shereen Oon, Nicholas J Wilson, Ian Wicks
Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by impaired immune tolerance, resulting in the generation of pathogenic autoantibodies and immune complexes. Although autoreactive B lymphocytes have been the first targets for biologic therapies in SLE, the importance of the innate immune system, and in particular, pathways involved in interferon (IFN) signaling, has emerged. There are now data supporting a central role for a plasmacytoid dendritic cell-derived type I IFN pathway in SLE, with a number of biologic therapeutics and small-molecule inhibitors undergoing clinical trials...
May 2016: Clinical & Translational Immunology
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