Disordered Metabolism in Mice Lacking Irisin Yunyao Luo1,2,3,4,6, Xiaoyong Qiao1,2,3,4,6, Yaxian Ma1,2,3,4, Hongxia Deng1,2,3,4, Charles C
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Induction of a TRAIL Mediated Suicide Program by Interferon Alpha in Primary E€Usion Lymphoma
Oncogene (2001) 20, 7029 ± 7040 ã 2001 Nature Publishing Group All rights reserved 0950 ± 9232/01 $15.00 www.nature.com/onc Induction of a TRAIL mediated suicide program by interferon alpha in primary eusion lymphoma Ngoc L Toomey1,4, Vadim V Deyev2,4, Charles Wood3, Lawrence H Boise2, Duncan Scott1, Lei Hua Liu1, Lisa Cabral1, Eckhard R Podack2, Glen N Barber2 and William J Harrington Jr*,1 1Department of Medicine University of Miami School of Medicine, Miami, Florida, FL 33136, USA; 2Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, Florida, FL 33136, USA; 3School of Biological Sciences, University of Nebraska, Lincoln, Nebraska, NE 68588, USA Gammaherpes viruses are often detected in lymphomas Virus (EBV) or Human Herpes Virus Type 8 (HHV-8) arising in immunocompromised patients. We have found have been isolated from lymphomas found in im- that Azidothymidine (AZT) alone induces apoptosis in munosuppressed organ transplant recipients, children Epstein Barr Virus (EBV) positive Burkitt's lymphoma with hereditary immunode®ciencies and patients with (BL) cells but requires interferon alpha (IFN-a) to induce acquired immunode®ciency (AIDS) (Swinnen, 1999; apoptosis in Human Herpes Virus Type 8 (HHV-8) Goldsby and Carroll, 1998; Knowles, 1999). Many of positive Primary Eusion Lymphomas (PEL). Our these tumors can be categorized into distinct subtypes analysis of a series of AIDS lymphomas revealed that based on a variety of morphologic and molecular IFN-a selectively induced very high levels of the Death criteria. For example, AIDS associated large cell Receptor (DR) tumor necrosis factor-related apoptosis- diuse or immunoblastic lymphomas (DLCL, IBL) inducing ligand (TRAIL) in HHV-8 positive PEL lines are often EBV positive while AIDS associated Burkitt's and primary tumor cells whereas little or no induction lymphomas (BL) less frequently contain EBV (Gaidano was observed in primary EBV+ AIDS lymphomas and et al., 1994). -
Porvac® Subunit Vaccine E2-CD154 Induces Remarkable Rapid Protection Against Classical Swine Fever Virus
Article Porvac® Subunit Vaccine E2-CD154 Induces Remarkable Rapid Protection against Classical Swine Fever Virus Yusmel Sordo-Puga 1, Marisela Suárez-Pedroso 1 , Paula Naranjo-Valdéz 2, Danny Pérez-Pérez 1, Elaine Santana-Rodríguez 1, Talia Sardinas-Gonzalez 1, Mary Karla Mendez-Orta 1, Carlos A. Duarte-Cano 1, Mario Pablo Estrada-Garcia 1 and María Pilar Rodríguez-Moltó 1,* 1 Animal Biotechnology Department, Center for Genetic Engineering and Biotechnology, P.O. Box 6162, Havana 10600, Cuba; [email protected] (Y.S.-P.); [email protected] (M.S.-P.); [email protected] (D.P.-P.); [email protected] (E.S.-R.); [email protected] (T.S.-G.); [email protected] (M.K.M.O.); [email protected] (C.A.D.); [email protected] (M.P.E.) 2 Central Laboratory Unit for Animal Health (ULCSA), Havana 11400, Cuba; [email protected] * Correspondence: [email protected]; Tel.: +53-7-2504419 Abstract: Live attenuated C-strain classical swine fever vaccines provide early onset protection. These vaccines confer effective protection against the disease at 5–7 days post-vaccination. It was previously reported that intramuscular administration of the Porvac® vaccine protects against highly virulent Citation: Sordo-Puga, Y.; classical swine fever virus (CSFV) “Margarita” strain as early as seven days post-vaccination. In Suárez-Pedroso, M.; Naranjo-Valdéz, order to identify how rapidly protection against CSFV is conferred after a single dose of the Porvac® P.; Pérez-Pérez, D.; subunit vaccine E2-CD154, 15 swine, vaccinated with a single dose of Porvac®, were challenged Santana-Rodríguez, E.; 3 intranasally at five, three, and one day post-vaccination with 2 × 10 LD50 of the highly pathogenic Sardinas-Gonzalez, T.; Mendez-Orta, Cuban “Margarita” strain of the classical swine fever virus. -
Age- and Gender-Specific Modulation of Serum Osteopontin and Interferon-Α by Osteopontin Genotype in Systemic Lupus Er
Genes and Immunity (2009) 10, 487–494 & 2009 Macmillan Publishers Limited All rights reserved 1466-4879/09 $32.00 www.nature.com/gene ORIGINAL ARTICLE Age- and gender-specific modulation of serum osteopontin and interferon-a by osteopontin genotype in systemic lupus erythematosus SN Kariuki1, JG Moore1, KA Kirou2,MKCrow2, TO Utset1 and TB Niewold1 1Section of Rheumatology, University of Chicago, Chicago, IL, USA and 2Mary Kirkland Center for Lupus Research, Hospital for Special Surgery, New York, NY, USA Osteopontin (OPN) is a multifunctional cytokine involved in long bone remodeling and immune system signaling. Additionally, OPN is critical for interferon-a (IFN-a) production in murine plasmacytoid dendritic cells. We have previously shown that IFN-a is a heritable risk factor for systemic lupus erythematosus (SLE). Genetic variants of OPN have been associated with SLE susceptibility, and one study suggests that this association is particular to men. In this study, the 3 0 UTR SLE-risk variant of OPN (rs9138C) was associated with higher serum OPN and IFN-a in men (P ¼ 0.0062 and P ¼ 0.0087, respectively). In women, the association between rs9138 C and higher serum OPN and IFN-a was restricted to younger subjects, and risk allele carriers showed a strong age-related genetic effect of rs9138 genotype on both serum OPN and IFN-a (Po0.0001). In African- American subjects, the 5 0 region single nucleotide polymorphisms, rs11730582 and rs28357094, were associated with anti- RNP antibodies (odds ratio (OR) ¼ 2.9, P ¼ 0.0038 and OR ¼ 3.9, P ¼ 0.021, respectively). Thus, we demonstrate two distinct genetic influences of OPN on serum protein traits in SLE patients, which correspond to previously reported SLE-risk variants. -
Interferon-Γ Enhances Interleukin 12 Production in Rheumatoid Synovial
Interferon-γ Enhances Interleukin 12 Production in Rheumatoid Synovial Cells via CD40-CD154 Dependent and Independent Pathways MINETAKE KITAGAWA, HIROSHI SUZUKI, YOSHIHIRO ADACHI, HIROSHI NAKAMURA, SHINICHI YOSHINO, and TAKAYUKI SUMIDA ABSTRACT. Objective. To determine the role of interferon-γ (IFN-γ) in CD40-CD154 dependent production of interleukin 12 (IL-12) by synovial cells of patients with rheumatoid arthritis (RA). Methods. We examined the effects of IFN-γ, tumor necrosis factor-α (TNF-α), and granulocyte- macrophage colony stimulating factor (GM-CSF) on CD40 expression on CD68+ synovial macrophage-lineage cells (SMC). The effects of IFN-γ and soluble CD154 (sCD154) on IL-12 production by RA synovial cells were determined by ELISA. Results. CD68+ SMC expressed substantial levels of CD40. IFN-γ, but not TNF-α or GM-CSF, markedly upregulated CD40 expression on CD68+ SMC. IFN-γ also dose dependently increased IL- γ 12 production by synovial cells. The effects of IFN- on CD40 expression (EC50 = 127.4 U/ml) were observed at a concentration 19 times lower than the effects on IL-12 production (EC50 = 6.8 U/ml). Treatment with IFN-γ at a concentration low enough to augment CD40 expression but not IL-12 production enhanced spontaneous IL-12 production synergy with sCD154. The synergistic enhance- ment of spontaneous IL-12 production was abrogated by CD40-Fc. In contrast, IL-12 production induced by high concentration of IFN-γ was not neutralized by CD40-Fc. Conclusion. IFN-γ enhanced IL-12 production via both CD40-CD154 dependent and independent pathways in RA synovium. IFN-γ may play a crucial role in the development of RA synovitis through regulation of IL-12 production. -
Dysregulated Interferon Response Underlying Severe COVID-19
viruses Review Dysregulated Interferon Response Underlying Severe COVID-19 LeAnn Lopez y, Peter C. Sang y, Yun Tian y and Yongming Sang * Department of Agricultural and Environmental Sciences, College of Agriculture, Tennessee State University, 3500 John A. Merritt Boulevard, Nashville, TN 37209, USA; [email protected] (L.L.); [email protected] (P.C.S.); [email protected] (Y.T.) * Correspondence: [email protected]; Tel.: +1-615-963-5183 These authors contributed equally. y Academic Editor: Andrew Davidson Received: 27 October 2020; Accepted: 9 December 2020; Published: 13 December 2020 Abstract: Innate immune interferons (IFNs), including type I and III IFNs, constitute critical antiviral mechanisms. Recent studies reveal that IFN dysregulation is key to determine COVID-19 pathogenesis. Effective IFN stimulation or prophylactic administration of IFNs at the early stage prior to severe COVID-19 may elicit an autonomous antiviral state, restrict the virus infection, and prevent COVID-19 progression. Inborn genetic flaws and autoreactive antibodies that block IFN response have been significantly associated with about 14% of patients with life-threatening COVID-19 pneumonia. In most severe COVID-19 patients without genetic errors in IFN-relevant gene loci, IFN dysregulation is progressively worsened and associated with the situation of pro-inflammation and immunopathy, which is prone to autoimmunity. In addition, the high correlation of severe COVID-19 with seniority, males, and individuals with pre-existing comorbidities will be plausibly explained by the coincidence of IFN aberrance in these situations. Collectively, current studies call for a better understanding of the IFN response regarding the spatiotemporal determination and subtype-specificity against SARS-CoV-2 infections, which are warranted to devise IFN-related prophylactics and therapies. -
Molecular Mechanisms Underlying the Beneficial Effects of Exercise On
International Journal of Molecular Sciences Review Molecular Mechanisms Underlying the Beneficial Effects of Exercise on Brain Function and Neurological Disorders Kévin Nay 1,2, William J. Smiles 1 , Jacqueline Kaiser 1, Luke M. McAloon 1,2, Kim Loh 1,3, Sandra Galic 1, Jonathan S. Oakhill 1,2, Andrew L. Gundlach 3,4 and John W. Scott 1,2,4,* 1 St Vincent’s Institute of Medical Research, Fitzroy, Victoria 3065, Australia; [email protected] (K.N.); [email protected] (W.J.S.); [email protected] (J.K.); [email protected] (L.M.M.); [email protected] (K.L.); [email protected] (S.G.); [email protected] (J.S.O.) 2 Exercise and Nutrition Research Program, Mary MacKillop Institute for Health Research, Australian Catholic University, Melbourne, Victoria 3000, Australia 3 Department of Medicine, University of Melbourne, Parkville, Victoria 3010, Australia; andrew.gundlach@florey.edu.au 4 The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria 3052, Australia * Correspondence: [email protected]; Tel.: +61-3-9288-3632 Abstract: As life expectancy has increased, particularly in developed countries, due to medical advances and increased prosperity, age-related neurological diseases and mental health disorders have become more prevalent health issues, reducing the well-being and quality of life of sufferers and their families. In recent decades, due to reduced work-related levels of physical activity, and key research insights, prescribing adequate exercise has become an innovative strategy to prevent or delay the onset of these pathologies and has been demonstrated to have therapeutic benefits when used Citation: Nay, K.; Smiles, W.J.; as a sole or combination treatment. -
Current Evidence of the Role of the Myokine Irisin in Cancer
cancers Review Current Evidence of the Role of the Myokine Irisin in Cancer Evangelia Tsiani 1,2,*, Nicole Tsakiridis 1, Rozalia Kouvelioti 1,3, Alina Jaglanian 1 and Panagiota Klentrou 2,3 1 Department of Health Sciences, Brock University, St. Catharines, ON L2S 3A1, Canada; [email protected] (N.T.); [email protected] (R.K.); [email protected] (A.J.) 2 Centre for Bone and Muscle Health, Brock University, St. Catharines, ON L2S 3A1, Canada; [email protected] 3 Department of Kinesiology, Brock University, St. Catharines, ON L2S 3A1, Canada * Correspondence: [email protected] Simple Summary: Regular exercise/physical activity is beneficial for the health of an individual and lowers the risk of getting different diseases, including cancer. How exactly exercise results in these health benefits is not known. Recent studies suggest that the molecule irisin released by muscles into the blood stream after exercise may be responsible for these effects. This review summarizes all the available in vitro/cell culture, animal and human studies that have investigated the relationship between cancer and irisin with the aim to shed light and understand the possible role of irisin in cancer. The majority of the in vitro studies indicate anticancer properties of irisin, but more animal and human studies are required to better understand the exact role of irisin in cancer. Abstract: Cancer is a disease associated with extreme human suffering, a huge economic cost to health systems, and is the second leading cause of death worldwide. Regular physical activity is associated with many health benefits, including reduced cancer risk. In the past two decades, exercising/contracting skeletal muscles have been found to secrete a wide range of biologically active proteins, named myokines. -
FNDC5 Gene Interactions with Candidate Genes FOXOA3 and AP
The Author(s) BMC Genomics 2017, 18(Suppl 8):803 DOI 10.1186/s12864-017-4194-4 RESEARCH Open Access Epistasis, physical capacity-related genes and exceptional longevity: FNDC5 gene interactions with candidate genes FOXOA3 and APOE Noriyuki Fuku1*†, Roberto Díaz-Peña2,3†, Yasumichi Arai4, Yukiko Abe4, Hirofumi Zempo1, Hisashi Naito1, Haruka Murakami5, Motohiko Miyachi5, Carlos Spuch6, José A. Serra-Rexach8, Enzo Emanuele7, Nobuyoshi Hirose1 and Alejandro Lucia9 From 34th FIMS World Sports Medicine Congress Ljubljana, Slovenia. 29th September – 2nd October 2016 Abstract Background: Forkhead box O3A (FOXOA3) and apolipoprotein E (APOE) are arguably the strongest gene candidates to influence human exceptional longevity (EL, i.e., being a centenarian), but inconsistency exists among cohorts. Epistasis, defined as the effect of one locus being dependent on the presence of ‘modifier genes’,maycontributeto explain the missing heritability of complex phenotypes such as EL. We assessed the potential association of epistasis among candidate polymorphisms related to physical capacity, as well as antioxidant defense and cardiometabolic traits, and EL in the Japanese population. A total of 1565 individuals were studied, subdivided into 822 middle-aged controls and 743 centenarians. Results: We found a FOXOA3 rs2802292 T-allele-dependent association of fibronectin type III domain-containing 5 (FDNC5) rs16835198 with EL: the frequency of carriers of the FOXOA3 rs2802292 T-allele among individuals with the rs16835198 GG genotype was significantly higher in cases than in controls (P < 0.05). On the other hand, among non- carriers of the APOE ‘risk’ ε4-allele, the frequency of the FDNC5 rs16835198 G-allele was higher in cases than in controls (48.4% vs. -
NIH Public Access Author Manuscript Nature
NIH Public Access Author Manuscript Nature. Author manuscript; available in PMC 2012 December 14. Published in final edited form as: Nature. ; 481(7382): 463–468. doi:10.1038/nature10777. A PGC1α-dependent myokine that drives browning of white fat and thermogenesis $watermark-text $watermark-text $watermark-text Pontus Boström1, Jun Wu1, Mark P. Jedrychowski2, Anisha Korde1, Li Ye1, James C. Lo1, Kyle A. Rasbach1, Elisabeth Almer Boström3, Jang Hyun Choi1, Jonathan Z. Long1, Shingo Kajimura4, Maria Cristina Zingaretti5, Birgitte F. Vind6, Hua Tu7, Saverio Cinti5, Kurt Højlund6, Steven P. Gygi2, and Bruce M. Spiegelman1,* 1Dana-Farber Cancer Institute and Harvard Medical School, 3 Blackfan Circle, CLS Building, floor 11, Boston, MA, 02115, USA 2Department of Cell Biology, Harvard Medical School, Boston, MA, 02115, USA 3Renal Division, Brigham and Women’s Hospital, Harvard Medical School 4UCSF Diabetes Center and Department of Cell and Tissue Biology, University of California, San Francisco 5Department of Experimental and Clinical Medicine, Università Politecnica delle Marche, Electron Microscopy Unit-Azienda Ospedali Riuniti, Ancona 60020, Italy 6Diabetes Research Center, Department of Endocrinology, Odense University Hospital, Denmark 7LakePharma, Inc. 530 Harbor Blvd, Belmont CA 94002 Abstract Exercise benefits a variety of organ systems in mammals, and some of the best-recognized effects of exercise on muscle are mediated by the transcriptional coactivator PGC1α Here we show that PGC1α expression in muscle stimulates an increase in expression of Fndc5, a membrane protein that is cleaved and secreted as a new hormone, irisin. Irisin acts on white adipose cells in culture and in vivo to stimulate UCP1 expression and a broad program of brown fat-like development. -
Pegasys, INN-Peginterferon Alfa-2A
SCIENTIFIC DISCUSSION This module reflects the initial scientific discussion and scientific discussion on procedures, which have been finalised before 1 April 2005. For scientific information on procedures after this date please refer to module 8B. 1. Introduction Peginterferon alfa-2a is a polyethylene glycol (PEG)-modified form of human recombinant interferon alfa-2a intended for the treatment of adult patients with chronic hepatitis C (CHC) or chronic hepatitis B (CHB). Chronic hepatitis C is a major public health problem: hepatitis C virus (HCV) is responsible for a large proportion of chronic liver disease, accounting for 70% of cases of chronic hepatitis in industrialised countries. Globally there are an estimated 150 million chronic carriers of the virus, including 5 million in Western Europe. Without treatment approximately 30% of those infected with HCV will develop cirrhosis over a time frame of 30 years or more. For those with HCV-related cirrhosis, the prognosis is poor – a significant proportion will develop a life-threatening complication (either decompensated liver disease or an hepatocellular carcinoma) within a few years. The only therapy for those with advanced cirrhosis is liver transplantation, which carries a high mortality. In those who survive transplantation, viral recurrence in the new liver is almost inevitable and a significant proportion of infected liver grafts develop a progressive fibrosis that leads to recurrence of cirrhosis within 5 years. Interferon alfa monotherapy has been shown to be effective for the treatment of chronic hepatitis although sustained response rates occurred in approximately 15 to 30 % of patients treated for long duration (12-18 months). The current reference therapy is interferon alpha in combination with ribavirin, which resulted in an increase in biochemical and virological sustained response rates to approximately 40 % in naïve patients. -
The Acute Effects of Swimming Exercise on PGC-1-FNDC5/Irisin
H OH metabolites OH Article The Acute Effects of Swimming Exercise on PGC-1α-FNDC5/Irisin-UCP1 Expression in Male C57BL/6J Mice Eunhee Cho 1, Da Yeon Jeong 2, Jae Geun Kim 2,3 and Sewon Lee 4,5,6,* 1 Department of Human Movement Science, Graduate School, Incheon National University, Incheon 22012, Korea; [email protected] 2 Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon 22012, Korea; [email protected] (D.Y.J.); [email protected] (J.G.K.) 3 Institute for New Drug Development, Division of Life Sciences, Incheon National University, Incheon 22012, Korea 4 Division of Sport Science, College of Arts & Physical Education, Incheon National University, Incheon 22012, Korea 5 Sport Science Institute, College of Arts & Physical Education, Incheon National University, Incheon 22012, Korea 6 Health Promotion Center, College of Arts & Physical Education, Incheon National University, Incheon 22012, Korea * Correspondence: [email protected]; Tel.:+82-32-835-8572 Abstract: Irisin is a myokine primarily secreted by skeletal muscles and is known as an exercise- induced hormone. The purpose of this study was to determine whether the PGC-1α -FNDC5 /Irisin- UCP1 expression which is an irisin-related signaling pathway, is activated by an acute swimming exercise. Fourteen to sixteen weeks old male C57BL/6J mice (n = 20) were divided into control (CON, n n = 10) and swimming exercise groups (SEG, = 10). The SEG mice performed 90 min of acute swimming exercise, while control (non-exercised) mice were exposed to shallow water (2 cm of depth) for 90 min. -
Irisin – a Myth Rather Than An
OPEN Irisin – a myth rather than an SUBJECT AREAS: exercise-inducible myokine TRANSCRIPTION Elke Albrecht1*, Frode Norheim2*, Bernd Thiede3, Torgeir Holen2, Tomoo Ohashi4, Lisa Schering1, FAT METABOLISM Sindre Lee2, Julia Brenmoehl5, Selina Thomas6, Christian A. Drevon2, Harold P. Erickson4 & Steffen Maak1 Received 1Institute for Muscle Biology and Growth, Leibniz Institute for Farm Animal Biology, D-18196 Dummerstorf, Germany, 2Department 8 December 2014 of Nutrition, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway, 3The Biotechnology Centre of Oslo, University of Oslo, 0317 Oslo, Norway, 4Department of Cell Biology, Duke University, Durham, NC 27710, USA, 5Institute of Accepted Genome Biology, Leibniz Institute for Farm Animal Biology, D-18196 Dummerstorf, Germany, 6Swiss Institute of Equine Medicine 9 February 2015 (ISME), Vetsuisse Faculty, University of Berne, 1580 Avenches, Switzerland. Published 9 March 2015 The myokine irisin is supposed to be cleaved from a transmembrane precursor, FNDC5 (fibronectin type III domain containing 5), and to mediate beneficial effects of exercise on human metabolism. However, evidence for irisin circulating in blood is largely based on commercial ELISA kits which are based on Correspondence and polyclonal antibodies (pAbs) not previously tested for cross-reacting serum proteins. We have analyzed four commercial pAbs by Western blotting, which revealed prominent cross-reactivity with non-specific requests for materials proteins in human and animal sera. Using recombinant glycosylated and non-glycosylated irisin as positive should be addressed to controls, we found no immune-reactive bands of the expected size in any biological samples. A FNDC5 S.M. (maak@fbn- signature was identified at ,20 kDa by mass spectrometry in human serum but was not detected by the dummerstorf.de) commercial pAbs tested.