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IFN-gamma signaling

Mark Yulis, Miguel Quiros, Roland Hilgarth, Charles A Parkos, Asma Nusrat
Desmosomal cadherins mediate intercellular adhesion and have also been shown to regulate homeostatic signaling in epithelial cells. We have previously reported that select pro-inflammatory cytokines induce Dsg2 ectodomain cleavage and shedding from intestinal epithelial cells (IECs). Dsg2 extracellular cleaved fragments (Dsg2 ECF) function to induce paracrine pro-proliferative signaling in epithelial cells. In this study, we show that exposure of IECs to pro-inflammatory cytokines interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) resulted in Dsg2 intracellular cleavage and generation of a ~55 kDa fragment (Dsg2 ICF)...
March 9, 2018: Cell Death & Disease
Xiaoling Xie, Weijun Zhou, Yuxing Hu, Yiran Chen, Honghao Zhang, Yuhua Li
The identification and characterization of tumor-associated antigens (TAAs) that generate specific cytotoxic T lymphocytes (CTLs) are vital to the development of cancer immunotherapy. The epidermal growth factor receptor (EGFR) pathway substrate 8 gene (Eps8) is involved in regulating cancer progression and might be an ideal antigen. In this study, we searched for novel human leukocyte antigen (HLA)-A*2402-restricted epitopes derived from the Eps8 protein via the HLA-binding prediction algorithm. Among four candidates, peptides 327 (EFLDCFQKF), 534 (KYAKSKYDF) and 755 (LFSLNKDEL) induced peptide-specific CTLs to secrete higher levels of interferon-gamma (IFN-γ) and showed enhanced cytotoxic activity against malignant cancer cells...
March 7, 2018: Cell Death & Disease
Ai-Ling Tian, MingMin Lu, Guillermo Calderón-Mantilla, Evangelia Petsalaki, Tania Dottorini, XiaoWei Tian, YuJian Wang, Si-Yang Huang, Jun-Ling Hou, XiangRui Li, Hany M Elsheikha, Xing-Quan Zhu
BACKGROUND: The molecular structure of Fasciola gigantica 14-3-3 protein has been characterized. However, the involvement of this protein in parasite pathogenesis remains elusive and its effect on the functions of innate immune cells is unknown. We report on the cloning and expression of a recombinant F. gigantica 14-3-3 epsilon protein (rFg14-3-3e), and testing its effects on specific functions of goat peripheral blood mononuclear cells (PBMCs). METHODS: rFg14-3-3e protein was expressed in Pichia pastoris...
March 6, 2018: Parasites & Vectors
Fen Zhao, Yonghui Yu, Wei Liu, Jian Zhang, Xinqi Liu, Huinan Yin, Liuling Ying
This article describes results of the effect of dietary supplementation with small molecular weight soybean protein-derived peptides on major rat burn injury-induced muscle atrophy. As protein nutrients have been previously implicated to play an important role in improving burn injury outcomes, optimized more readily absorbed small molecular weight soybean protein-derived peptides were evaluated. Thus, the quantity, SDS-PAGE patterns, molecular weight distribution, and composition of amino acids of the prepared peptides were analyzed, and a major full-thickness 30% total body surface area (TBSA) burn-injury rat model was utilized to assess the impact of supplementation with soybean protein-derived peptides on initial systemic inflammatory responses as measured by interferon-gamma (IFN-γ), chemokine (C-C motif) ligand 2 (CCL2, also known as MCP-1), chemokine (C-C motif) ligand 7 (CCL7, also known as MCP-3) and generation of muscle atrophy as measured by tibialis anterior muscle (TAM) weight relative to total body weight...
March 1, 2018: Journal of Agricultural and Food Chemistry
Min Yu, Qimeng Wang, Yuanhang Ma, Liangzi Li, Kun Yu, Zhicao Zhang, Guoqing Chen, Xiangsheng Li, Weidong Xiao, Pengyuan Xu, Hua Yang
Activation of Aryl hydrocarbon receptor (AhR) is involved in the control of intestinal mucosal homeostasis. Intestinal barrier dysfunction contributes to the development of many intestinal diseases, such as inflammatory bowel disease (IBD). In this study, we investigated the mechanisms of AhR activation in the maintenance of intestinal barrier function. Adult C57BL/6 mice were treated with dextran sulphate sodium (DSS) for 7 days, with or without 6-Formylindolo(3,2-b)carbazole (FICZ), a ligand of AhR. We found that AhR activation by FICZ attenuated the decreased TJ protein expression in the colonic mucosa of the DSS-induced mice...
2018: International Journal of Biological Sciences
Benjamin D S Clarkson, Misha S Patel, Reghann G LaFrance-Corey, Charles L Howe
Objective: Injury-associated axon-intrinsic signals are thought to underlie pathogenesis and progression in many neuroinflammatory and neurodegenerative diseases, including multiple sclerosis (MS). Retrograde interferon gamma (IFN γ ) signals are known to induce expression of major histocompatibility class I (MHC I) genes in murine axons, thereby increasing the susceptibility of these axons to attack by antigen-specific CD8+ T cells. We sought to determine whether the same is true in human neurons...
February 2018: Annals of Clinical and Translational Neurology
Feilong Wang, Song Zhang, Ryounghoon Jeon, Ivan Vuckovic, Xintong Jiang, Amir Lerman, Clifford D Folmes, Petras D Dzeja, Joerg Herrmann
Classical activation of M1 macrophages with lipopolysaccharide (LPS) is associated with a metabolic switch from oxidative phosphorylation to glycolysis. However, the generalizability of such metabolic remodeling to other modes of M1 macrophage stimulation, e.g. type II interferons (IFNs) such as IFNγ, has remained unknown as has the functional significance of aerobic glycolysis during macrophage activation. Here we demonstrate that IFNγ induces a rapid activation of aerobic glycolysis followed by a reduction in oxidative phosphorylation in M1 macrophages...
February 13, 2018: EBioMedicine
Hamed Haddad Kashani, Elahe Seyed Hosseini, Hossein Nikzad, Alireza Soleimani, Maryam Soleimani, Mohammad Reza Tamadon, Fariba Keneshlou, Zatollah Asemi
Objective: This study was carried out to determine the effects of vitamin D supplementation on signaling pathway of inflammation and oxidative stress in diabetic hemodialysis (HD) patients. Methods: This randomized double-blind placebo-controlled clinical trial was conducted among 60 diabetic HD patients. Subjects were randomly allocated into two groups to intake either vitamin D supplements at a dosage of 50,000 IU ( n = 30) or placebo ( n = 30) every 2 weeks for 12 weeks. Gene expression of inflammatory cytokines and biomarkers of oxidative stress were assessed in peripheral blood mononuclear cells (PBMCs) of diabetic HD patients with RT-PCR method...
2018: Frontiers in Pharmacology
Zhongxiu Wang, Jingyi Tan, Lihong Lei, Weilian Sun, Yanmin Wu, Peihui Ding, Lili Chen
OBJECTIVE: Interleukin-17 (IL-17) and interferon-gamma (IFN-γ) are all pro-inflammatory cytokines produced by specific subsets of T-cells and are also considered crucial regulators in bone remodeling, but their effects on osteogenesis have not been carefully studied. So, this study aimed to investigate the effects of secreting cytokines IL-17 and IFN-γ on the osteogenesis of primary osteoblasts and to clarify the potential roles of the related Janus activated kinase 2 (JAK2) and downstream signal transducer and activator of transcription 3 (STAT3) signaling pathway in bone remodeling...
February 10, 2018: International Immunopharmacology
Zhongyang Xu, Xiuyu Wang, Yanping Zheng
Ankylosing spondylitis (AS) is a chronic inflammatory arthritis and autoimmune disease, the etiology and pathogenesis of which remain largely unknown. In the present study, blood samples were harvested from patients with AS and from healthy volunteers as a normal control (NC) for RNA-sequencing. Differentially expressed genes (DEGs) in the AS group compared with the NC group were identified, and gene ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were subsequently performed...
February 2018: Experimental and Therapeutic Medicine
Niki Karachaliou, Maria Gonzalez-Cao, Guillermo Crespo, Ana Drozdowskyj, Erika Aldeguer, Ana Gimenez-Capitan, Cristina Teixido, Miguel Angel Molina-Vila, Santiago Viteri, Maria De Los Llanos Gil, Salvador Martin Algarra, Elisabeth Perez-Ruiz, Ivan Marquez-Rodas, Delvys Rodriguez-Abreu, Remedios Blanco, Teresa Puertolas, Maria Angeles Royo, Rafael Rosell
Background: Programmed death-ligand 1 (PD-L1) may be induced by oncogenic signals or can be upregulated via interferon gamma (IFN-γ). We have explored whether the expression of IFNG, the gene encoding IFN-γ, is associated with clinical response to the immune checkpoint blockade in non-small cell lung cancer (NSCLC) and melanoma patients. The role of inflammation-associated transcription factors STAT3, IKBKE, STAT1 and other associated genes has also been examined. Methods: Total RNA from 17 NSCLC and 21 melanoma patients was analyzed by quantitative reverse transcription PCR...
2018: Therapeutic Advances in Medical Oncology
Ying Huang, Yuan Qi, JianQing Du, DaiFu Zhang
Objectives: Protosappanin A (PrA) is an effective and major ingredient of Caesalpinia sappan L. The current study was aimed to explore the effect of PrA on atherosclerosis (AS). Materials and Methods: Firstly, the experimental model of AS was established in rabbits by two-month feeding of high fat diet. Then, the rabbits were randomly divided into five groups and treated with continuous high lipid diet (model control), high lipid diet containing rosuvastatin (positive control), 5 mg/kg PrA (low dose) or 25 mg/kg PrA (high dose)...
January 2018: Iranian Journal of Basic Medical Sciences
Xue-Tao Huang, Bin Wang, Wen-Hua Zhang, Man-Qiang Peng, Ding Lin
Total glucosides of paeony (TGP) are active components extracted from the roots of Paeonia lactiflora Pall. In this study, we investigated the role and mechanisms of TGP in experimental autoimmune uveitis (EAU) model of mice. The C57BL/6 mice were randomly divided into three groups: sham group, EAU-control group, and EAU-TGP group. Clinical score of images of the eye fundus were taken on 7, 14, 21, and 28 days after induction of EAU. The concentrations of proinflammatory cytokines in intraocular fluid were measured at 14 days after EAU induction with the use of a multiplex assay system...
January 2018: International Journal of Immunopathology and Pharmacology
Ganesh V Shelke, Jayashree C Jagtap, Dae-Kyum Kim, Reecha D Shah, Gowry Das, Mruthyunjaya Shivayogi, Radha Pujari, Padma Shastry
The objective of this study was to examine the combined effect of Interferon-gamma (IFN-γ) and Tumor Necrosis factor-alpha (TNF-α) on cytotoxicity and expression of prostate apoptosis response-4 (Par-4) and Par-4 interacting proteins B-cell lymphoma (Bcl-2), nuclear factor kappa-light-chain-enhancer of activated B cells/p65 subunit (NF-κB/p65), Ak mouse strain thymoma (Akt) in human neuroblastoma (NB) cells. Materials and methods included human neuroblastoma cell lines-SK-N-MC, SK-N-SH, and SH-SY5Y, which were treated with IFN-γ and TNF-α individually, or in combination, and were assessed for viability by tetrazolium (MTT) assay...
December 26, 2017: Biomedicines
Alexander D Barrow, Melissa A Edeling, Vladimir Trifonov, Jingqin Luo, Piyush Goyal, Benjamin Bohl, Jennifer K Bando, Albert H Kim, John Walker, Mary Andahazy, Mattia Bugatti, Laura Melocchi, William Vermi, Daved H Fremont, Sarah Cox, Marina Cella, Christian Schmedt, Marco Colonna
Many tumors produce platelet-derived growth factor (PDGF)-DD, which promotes cellular proliferation, epithelial-mesenchymal transition, stromal reaction, and angiogenesis through autocrine and paracrine PDGFRβ signaling. By screening a secretome library, we found that the human immunoreceptor NKp44, encoded by NCR2 and expressed on natural killer (NK) cells and innate lymphoid cells, recognizes PDGF-DD. PDGF-DD engagement of NKp44 triggered NK cell secretion of interferon gamma (IFN)-γ and tumor necrosis factor alpha (TNF-α) that induced tumor cell growth arrest...
January 25, 2018: Cell
Yuji Nozaki, Shoichi Hino, Jinhai Ri, Kenji Sakai, Yasuaki Nagare, Mai Kawanishi, Kaoru Niki, Masanori Funauchi, Itaru Matsumura
The proinflammatory cytokine interleukin (IL)-18 is an important mediator of the organ failure induced by endotoxemia. IL-18 (known as an interferon-gamma (IFN-γ) inducing factor), and other inflammatory cytokines have important roles in lipopolysaccharide (LPS)-induced acute kidney injury (AKI). We investigated the effect of inflammatory cytokines and Toll-like receptor 4 (TLR4) expression, an event that is accompanied by an influx of monocytes, including CD4⁺ T cells and antigen-presenting cells (APCs) in IL-18Rα knockout (KO) mice and wild-type (WT) mice after LPS injection...
December 20, 2017: International Journal of Molecular Sciences
Rylend Mulder, Andra Banete, Kyle Seaver, Sameh Basta
CD8+ cytotoxic T cell (CTL) responses are necessary for the lysis of virally infected cells and control of infection. CTLs are activated when their TCRs bind a major histocompatibility complex (MHC)-I/peptide complex on the surface of antigen presenting cells such as macrophages (MΦ). It is now apparent that MΦ display remarkable plasticity in response to environmental signals to polarize into classically activated M(LPS + IFN-γ) or alternatively activated M(IL-4). However, little is known about how MΦ activation status influences their antigen presentation function to CD8+ T cell in models of virus infection...
2017: Frontiers in Immunology
Jennifer M Cassano, Lauren V Schnabel, Margaret B Goodale, Lisa A Fortier
Mesenchymal stem cells (MSCs) have the therapeutic potential to treat a variety of inflammatory and degenerative disease processes, however the effects of the tissue environment on MSCs have been overlooked. Our hypothesis was that the immunomodulatory function of MSCs would be impaired by TLR4 stimulation or exposure to inflammatory macrophages, whereas their immunosuppressive properties would be enhanced by TLR3 stimulation. MSCs were exposed to polyinosinic:polycytidylic acid (poly I:C) to stimulate TLR3 receptors or lipopolysaccharide (LPS) to stimulate TLR4 receptors...
January 2018: Veterinary Immunology and Immunopathology
Chiara Zini, Mary A Venneri, Selenia Miglietta, Damiano Caruso, Natale Porta, Andrea M Isidori, Daniela Fiore, Daniele Gianfrilli, Vincenzo Petrozza, Andrea Laghi
Aim of the study was to evaluate USPIO labeling in different macrophage populations using a clinical 3.0T MR unit with optical and electron microscopy as the gold standard. Human monocytic cell line THP-1 cells were differentiated into macrophages. Afterwards, M0 macrophages were incubated with IL-4 and IL-13 in order to obtain M2 polarized macrophages or with IFN-gamma and LPS for classical macrophage activation (M1). These groups were incubated with USPIO-MR contrast agent (P904) for 36 hr; M0, M0 + P904, M1 +  P904, and M2 + P904 were analyzed in gel phantoms with a 3...
December 12, 2017: Journal of Cellular Physiology
Sahin Sultana, Rajen Dey, Biswadev Bishayi
Severity of S. aureus septic arthritis is correlated to prolonged inflammation by inflammatory cytokines like TNF-α, IL-1β, and IL-6 even after successful elimination of bacteria. Role of TNF-α via TNFR2 is not well established in this aspect. IFN-γ induces TNF-α release from the macrophages augmenting the inflammatory arthritis. IL-10 modulates the levels of pro-inflammatory cytokines promoting resolution of inflammation. TNF-α-TNFR2 signaling upregulates both of these cytokines. Higher level of MMP-2 induction by inflammatory cytokines during arthritis promotes tissue destruction...
February 2018: Immunologic Research
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