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interferon beta

Jing Xue, Qinglan Zhao, Vishal Sharma, Linh P Nguyen, Yvonne N Lee, Kim L Pham, Mouad Edderkaoui, Stephen J Pandol, Walter Park, Aida Habtezion
BACKGROUND & AIMS: Cigarette smoke has been identified as an independent risk factor for chronic pancreatitis (CP). Little is known about the mechanisms by which smoking promotes development of CP. We assessed the effects of aryl hydrocarbon receptor (AhR) ligands found in cigarette smoke on immune cell activation in humans and pancreatic fibrosis in animal models of CP. METHODS: We obtained serum samples from patients with CP treated at Stanford University hospital and healthy individuals (controls) and isolated CD4+ T cells; levels of interleukin-22 (IL22) were measured by ELISA and smoking histories were collected...
October 18, 2016: Gastroenterology
Guiyou Liu, Fang Zhang, Yang Hu, Yongshuai Jiang, Zhongying Gong, Shoufeng Liu, Xiuju Chen, Qinghua Jiang, Junwei Hao
A recent genome-wide association study reported a significant association between rs9828519 (G) and nonresponsiveness to interferon-beta (IFN-β) treatment and dysregulation of SLC9A9 expression in multiple sclerosis (MS) cases. We hypothesize that disease-relevant tissues are necessary to detect the effects of rs9828519-tagged SNPs on SLC9A9 expression. Here, we investigated whether SLC9A9 expression is regulated by rs9828519-tagged SNPs in human brain tissue. We used HaploReg to identify the proxy SNPs of the rs9828519 variant based on linkage disequilibrium information from the 1000 Genomes Project...
October 20, 2016: Molecular Neurobiology
Afshin Fathi, Firuz Amani, Mohammad Davoodi, Sara Bahadoram, Mohammad Bahadoram
INTRODUCTION: Nasopharyngeal carcinoma among the children has been rare accounting for only 1% of all pediatric malignancies. Both genetic and environmental factors have contributed to the development of nasopharyngeal carcinoma. Among the children there was a higher rate of undifferentiated histology. The mean age of nasopharyngeal carcinoma diagnosis has been 11 years old age; and the most common site was nasopharynx. Palpable lymphadenopathy, dysphasia and neural defect were common associated signs...
August 2016: Iranian Journal of Cancer Prevention
Anna V Cherepanova, Zhanna K Nazarkina, Pavel P Laktionov
Oligodeoxynucleotide (ODN) analogues of cell-surface-bound circulating DNA inhibit the dsRNA-induced production of pro-inflammatory interleukin 6, interferon beta and antibacterial peptide beta-defensin 2 not only in human gingival fibroblasts, but also in human primary endothelial and transformed cells (Hela and A431). ODN analogues do not effect dendritic cells activation by poly(I:C). The data obtained indicate that the early stages of the signal transduction cascade are violated by ODN analogues and the effects depend on the cell type...
2016: Advances in Experimental Medicine and Biology
Naeim Ehtesham, Fariborz Khorvash, Majid Kheirollahi
MicroRNAs (miRNAs) are crucial to the immunopathogenesis of multiple sclerosis (MS). The mechanism of action of interferon beta (IFN-β) in relapsing-remitting (RR) MS patients is largely unknown. miR-145 and miR-20a-5p previously reported as diagnosis biomarker in treatment naïve RRMS patients and their expression after IFN-β therapy might be indicative of molecular mechanism of IFN-β. Cross-talking between JAK/STAT pathway and complementary pathways like MAPK is important in IFN-β signaling. Here, in order to clarify the ambiguous molecular mechanism of IFN-β and evaluate the potential use of them as a biomarker for monitoring of therapy, we investigated the expression of miR-145 and miR-20a-5p in blood sample of 15 treatment naïve RRMS patients, 15 IFN-β-treated RRMS patients, and 15 healthy volunteers (HVs)...
October 17, 2016: Journal of Molecular Neuroscience: MN
Rodrigo Fabrizzio Inácio, Renata Gacielle Zanon, Mateus Vidigal de Castro, Henrique Marques de Souza, Marcio Chaim Bajgelman, Liana Verinaud, Alexandre Leite Rodrigues de Oliveira
Astrocytes are multifunctional glial cells that actively participate in synaptic plasticity in health and disease. Little is known about molecular interactions between neurons and glial cells that result in synaptic stability or elimination. In this sense, the main histocompatibility complex of class I (MHC I) has been shown to play a role in the synaptic plasticity process during development and after lesion of the CNS. MHC I levels in neurons appear to be influenced by astrocyte secreted molecules, which may generate endoplasmic reticulum stress...
October 14, 2016: Neuroscience Letters
B Perlman, D Heller, B Cracchiolo
OBJECTIVE: Postmenopausal bleeding must always be evaluated to rule out endometrial carcinoma, although there are many benign etiologies. There have been rare reports of premenopausal bleeding with interferon beta-1b, used to treat multiple sclerosis, but no prior reports in postmenopausal women. METHODS: Literature searches were performed using PubMed and Medline for articles with content related to premenopausal and postmenopausal bleeding while taking interferon beta-1b...
October 17, 2016: Climacteric: the Journal of the International Menopause Society
Roi Isaac, Ido Goldstein, Noa Furth, Neta Zilber, Sarina Streim, Sigalit Boura-Halfon, Eytan Elhanany, Varda Rotter, Moshe Oren, Yehiel Zick
Earlier reported small interfering RNA (siRNA) high-throughput screens, identified seven-transmembrane superfamily member 3 (TM7SF3) as a novel inhibitor of pancreatic β-cell death. Here we show that TM7SF3 maintains protein homeostasis and promotes cell survival through attenuation of ER stress. Overexpression of TM7SF3 inhibits caspase 3/7 activation. In contrast, siRNA-mediated silencing of TM7SF3 accelerates ER stress and activation of the unfolded protein response (UPR). This involves inhibitory phosphorylation of eukaryotic translation initiation factor 2α activity and increased expression of activating transcription factor-3 (ATF3), ATF4 and C/EBP homologous protein, followed by induction of apoptosis...
October 14, 2016: Cell Death and Differentiation
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
Luis Hernandez, Shien Guo, Hector Toro-Diaz, Stuart Carroll, Syed Feisal Syed Farooq
AIMS: Peginterferon beta-1a 125 mcg administered subcutaneously every two weeks, a new disease-modifying therapy (DMT) for relapsing-remitting multiple sclerosis (RRMS), was approved in January 2015 by the Scottish Medicines Consortium. This study assesses long-term clinical and economic outcomes of peginterferon beta-1a compared with other self-injectable DMTs (interferon beta-1a [22 mcg, 30 mcg, and 44 mcg], interferon beta-1b, and glatiramer acetate 20 mg) in the treatment of RRMS, from the National Health Service and personal social services perspective in Scotland...
October 12, 2016: Journal of Medical Economics
Manishekhar Kumar, Jeannine M Coburn, David L Kaplan, Biman B Mandal
Macrophages, the key players in immunoregulation, are actively involved in tissue remodelling and vascularization. Recent advances in tissue engineering and regenerative medicine illustrate the importance of 'immuno-informed' biomaterials to regulate the microenvironment of biomedical implants. In the current study, silk-based 3D hydrogels were utilized to regulate cytokine delivery for macrophage, a type of immune cell, differentiation and polarization. Three different hydrogel variants, silk-poly(ethylene glycol) (PEG) (SP), silk-horseradish peroxidase (HRP) (SH) and silk-sonicated (SS) hydrogels were studied...
October 11, 2016: ACS Applied Materials & Interfaces
Xinchun Ye, Delian Kong, Jun Wang, Tauheed Ishrat, Hongjuan Shi, Xiaohui Ding, Guiyun Cui, Fang Hua
Myeloid differentiation primary-response protein-88 (MyD88) is one of adaptor proteins mediating Toll-like receptors (TLRs) signaling. Activation of MyD88 results in the activation of nuclear factor kappa B (NFκB) and the increase of inflammatory responses. Evidences have demonstrated that TLRs signaling contributes to cerebral ischemia/reperfusion (I/R) injury. However, the role of MyD88 in this mechanism of action is disputed and needs to be clarified. In the present study, in a mouse model of cerebral I/R, we examined the activities of NFκB and interferon factor-3 (IRF3), and the inflammatory responses in ischemic brain tissue using ELISA, Western blots, and real-time PCR...
October 4, 2016: Biochemical and Biophysical Research Communications
Sheena L Dupuy, Fariha Khalid, Brian C Healy, Sonya Bakshi, Mohit Neema, Shahamat Tauhid, Rohit Bakshi
BACKGROUND: Spinal cord atrophy occurs early in multiple sclerosis (MS) and impacts disability. The therapeutic effect of interferon beta-1a (IFNβ-1a) on spinal cord atrophy in patients with relapsing-remitting (RR) MS has not been explored. METHODS: We retrospectively identified 16 consecutive patients receiving weekly intramuscular IFNβ-1a for 2 years [baseline age (mean ± SD) 47.7 ± 7.5 years, Expanded Disability Status Scale score median (range) 1...
October 5, 2016: BMC Medical Imaging
Alessandra Bua, Melania Ruggeri, Stefania Zanetti, Paola Molicotti
Multiple sclerosis is a chronic inflammatory disease of the central nervous system characterized by damage to myelin and axons, over time leading to progressive neuronal degeneration and microglial activation. There is still no curative treatment, but during the last 20 years eight different therapies have become available including interferon beta, glatiramer acetate, teriflunomide, dimethyl fumarate, natalizumab, fingolimod, alemtuzumab, mitoxantrone and teriflunomide. Teriflunomide is an immunomodulatory drug that exerts an inhibitory effect on T cell activation in central nervous system of the patients with multiple sclerosis...
October 4, 2016: Medical Microbiology and Immunology
Michael B Cheung, Viviana Sampayo-Escobar, Ryan Green, Martin L Moore, Subhra Mohapatra, Shyam S Mohapatra
Respiratory syncytial virus (RSV) has been reported to infect human mesenchymal stem cells (MSCs) but the consequences are poorly understood. MSCs are present in nearly every organ including the nasal mucosa and the lung and play a role in regulating immune responses and mediating tissue repair. We sought to determine whether RSV infection of MSCs enhances their immune regulatory functions and contributes to RSV-associated lung disease. RSV was shown to replicate in human MSCs by fluorescence microscopy, plaque assay, and expression of RSV transcripts...
2016: PloS One
Dror S Shouval, Amlan Biswas, Yu Hui Kang, Alexandra E Griffith, Liza Konnikova, Ivan D Mascanfroni, Naresh S Redhu, Sandra M Frei, Michael Field, Andria L Doty, Jeffrey D Goldsmith, Atul K Bhan, Anthony Loizides, Batia Weiss, Baruch Yerushalmi, Tadahiro Yanagi, Xiuli Lui, Francisco J Quintana, Aleixo M Muise, Christoph Klein, Bruce H Horwitz, Sarah C Glover, Athos Bousvaros, Scott B Snapper
IL10 receptor (IL10R)-deficient mice develop spontaneous colitis and similarly, patients with loss-of-function mutations in IL10R develop severe infant-onset inflammatory bowel disease (IBD). Loss of IL10R signaling in mouse and human macrophages is associated with increased production of interleukin 1 beta (IL1B). We demonstrated that innate immune production of IL1B mediates colitis in IL10R-deficient mice. Transfer of Il1r1(-/-) CD4(+) T cells into Rag1-/-/Il10rb-/- mice reduced the severity of their colitis (compared to mice that received CD4(+) T cells that express IL1R), accompanied by decreased production of interferon gamma, tumor necrosis factor, and IL17A...
September 27, 2016: Gastroenterology
Marzieh Khoshbin Nazdik, Mohammad Taheri, Mir Davood Omrani, Elham Sajjadi, Shahram Arsang-Jang, Zeinab Kazaei Koohpar, Hidetoshi Inoko, Arezou Sayad
OBJECTIVES: Multiple sclerosis (MS) is an autoimmune disease involving the central nervous system (CNS) with unknown immunopathogenic mechanisms. Matrix metalloproteinase-9 (MMP-9) facilitates T-cell migration into the CNS while the tissue inhibitor matrix metalloproteinase-1 (TIMP-1) inhibits MMP-9 actions. The aim of this study was to evaluate the expression of TIMP-1 RNA and MMP-9/TIMP-1 RNA ratio in blood cells of Iranian patients with relapsing-remitting multiple sclerosis (RRMS) treated with IFNb...
September 22, 2016: Human Antibodies
Brandon J Dixon, Di Chen, Yang Zhang, Jerry Flores, Jay Malaguit, Derek Nowrangi, John H Zhang, Jiping Tang
Neonatal hypoxic-ischemic encephalopathy (HIE) is an injury that often leads to detrimental neurological deficits. Currently, there are no established therapies for HIE and it is critical to develop treatments that provide protection after HIE. The objective of this study was to investigate the ability of interferon beta (IFNβ) to provide neuroprotection and reduce apoptosis after HIE. Postnatal Day 10 rat pups were subjected to unilateral carotid artery ligation followed by 2.5 hr of exposure to hypoxia (8% O2)...
October 2016: ASN Neuro
Michael John Patton, Stuart McCorrister, Chris Grant, Garrett Westmacott, Robert Fariss, Pingzhao Hu, Kaiqiong Zhao, Mary Blake, Bill Whitmire, Chunfu Yang, Harlan D Caldwell, Grant McClarty
: The chlamydial protease-like activity factor (CPAF) is hypothesized to be an important secreted virulence factor; however, challenges in denaturing its proteolytic activity have hampered attempts to identify its legitimate targets. Here, we use a genetic and proteomic approach to identify authentic CPAF targets. Human epithelial cells infected with CPAF-sufficient and CPAF-deficient chlamydiae were lysed using known CPAF-denaturing conditions. Their protein profiles were analyzed using isobaric mass tags and liquid chromatography-tandem mass spectrometry...
September 27, 2016: MBio
Stanley Cohan
Despite the availability of multiple disease-modifying therapies for relapsing multiple sclerosis (MS), there remains a need for highly efficacious targeted therapy with a favorable benefit-risk profile and attributes that encourage a high level of treatment adherence. Daclizumab is a humanized monoclonal antibody directed against CD25, the α subunit of the high-affinity interleukin 2 (IL-2) receptor, that reversibly modulates IL-2 signaling. Daclizumab treatment leads to antagonism of proinflammatory, activated T lymphocyte function and expansion of immunoregulatory CD56(bright) natural killer cells, and has the potential to, at least in part, rectify the imbalance between immune tolerance and autoimmunity in relapsing MS...
2016: Biologics: Targets & Therapy
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