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Cibinetide dampens innate immune cell functions thus ameliorating the course of experimental colitis.
Nairz, Manfred; Haschka, David; Dichtl, Stefanie; Sonnweber, Thomas; Schroll, Andrea; Aßhoff, Malte; Mindur, John E; Moser, Patrizia L; Wolf, Dominik; Swirski, Filip K; Theurl, Igor; Cerami, Anthony; Brines, Michael; Weiss, Günter.
Afiliación
  • Nairz M; Department of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Pneumology, Medical University Innsbruck, Innsbruck, Austria. manfred.nairz@i-med.ac.at.
  • Haschka D; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. manfred.nairz@i-med.ac.at.
  • Dichtl S; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. manfred.nairz@i-med.ac.at.
  • Sonnweber T; Department of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Pneumology, Medical University Innsbruck, Innsbruck, Austria.
  • Schroll A; Department of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Pneumology, Medical University Innsbruck, Innsbruck, Austria.
  • Aßhoff M; Department of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Pneumology, Medical University Innsbruck, Innsbruck, Austria.
  • Mindur JE; Department of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Pneumology, Medical University Innsbruck, Innsbruck, Austria.
  • Moser PL; Department of Internal Medicine II, Infectious Diseases, Immunology, Rheumatology, Pneumology, Medical University Innsbruck, Innsbruck, Austria.
  • Wolf D; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Swirski FK; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Theurl I; Department of Pathology, Medical University of Innsbruck, Innsbruck, Austria.
  • Cerami A; Medical Clinic III for Oncology, Hematology, Immunoncology and Rheumatology, University Hospital Bonn, Bonn, Germany.
  • Brines M; Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Weiss G; Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Sci Rep ; 7(1): 13012, 2017 10 12.
Article en En | MEDLINE | ID: mdl-29026145
Two distinct forms of the erythropoietin receptor (EPOR) mediate the cellular responses to erythropoietin (EPO) in different tissues. EPOR homodimers signal to promote the maturation of erythroid progenitor cells. In other cell types, including immune cells, EPOR and the ß-common receptor (CD131) form heteromers (the innate repair receptor; IRR), and exert tissue protective effects. We used dextran sulphate sodium (DSS) to induce colitis in C57BL/6 N mice. Once colitis was established, mice were treated with solvent, EPO or the selective IRR agonist cibinetide. We found that both cibinetide and EPO ameliorated the clinical course of experimental colitis in mice, resulting in improved weight gain and survival. Correspondingly, DSS-exposed mice treated with cibinetide or EPO displayed preserved tissue integrity due to reduced infiltration of myeloid cells and diminished production of pro-inflammatory disease mediators including cytokines, chemokines and nitric oxide synthase-2. Experiments using LPS-activated primary macrophages revealed that the anti-inflammatory effects of cibinetide were dependent on CD131 and JAK2 functionality and were mediated via inhibition of NF-κB subunit p65 activity. Cibinetide activation of the IRR exerts potent anti-inflammatory effects, especially within the myeloid population, reduces disease activity and mortality in mice. Cibinetide thus holds promise as novel disease-modifying therapeutic of inflammatory bowel disease.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Oligopéptidos / Colitis / Progresión de la Enfermedad / Inmunidad Innata Límite: Animals / Female / Humans / Male Idioma: En Revista: Sci Rep Año: 2017 Tipo del documento: Article País de afiliación: Austria

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Oligopéptidos / Colitis / Progresión de la Enfermedad / Inmunidad Innata Límite: Animals / Female / Humans / Male Idioma: En Revista: Sci Rep Año: 2017 Tipo del documento: Article País de afiliación: Austria