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Comparative proteomic analysis of growth hormone secretagogue A233 treatment of murine macrophage cells J774A.2 indicates it has a role in antiviral innate response
Authors:Rebeca Martínez  Teresa Núñez de Villavicencio-Díaz  Aniel Sánchez  Yassel Ramos  Jesús Noda Ferro  Lázaro Gil González  Milagros Méndez  Elsa Rodríguez  Ernesto Marcos  Belinda Sánchez  Yordanka Masforrol  Hilda Garay  Fernando Albericio  Lisset Hermida  Luis Javier González  Eva Vonasek  Mario P Estrada  Vladimir Besada
Affiliation:1. Animal Biotechnology Division, Center for Genetic Engineering and Biotechnology, P.O. Box 6162, Havana 10600, Cuba;2. Department of Systems Biology, Center for Genetic Engineering and Biotechnology, Havana, Cuba;3. Vaccines Division, Center for Genetic Engineering and Biotechnology, Havana, Cuba;4. Proteomics Unit, Department of Structural Biology, Venezuelan Institute for Scientific Research, PO Box 20632, Caracas, Venezuela;5. Center for Molecular Immunology, Havana, Cuba;6. Synthetic Peptides Group, Physics and Chemistry Department, Center for Genetic Engineering and Biotechnology, Havana, Cuba;7. Department of Organic Chemistry, University of Barcelona, 08028 Barcelona, Spain
Abstract:BackgroundGrowth hormone secretagogues (GHS), among other factors, regulate the release of GH. The biological activity of the secretagogue peptide A233 as a promoter of growth and innate immunity in teleost fish has previously been demonstrated, but its role in the immune system of mammals is not well understood.MethodsThe effect of the peptide was investigated in J774A.2 macrophage cells using a comparative proteomics approach after 6 and 12 h of peptide stimulation.ResultsThe functional analysis of differentially modulated proteins showed that A233 peptide treatment appears to promote activation and ROS-dependent cytotoxic functions in macrophages and enhanced expression of antiviral protein complexes such as MAVS. In accordance with this hypothesis, we found that A233 treatment enhanced superoxide anion production and the IFN-γ level in J774A.2 cells and mouse splenocytes, respectively, and reduced viral load in a dengue virus mouse model of infection.ConclusionsThe growth hormone secretagogue A233 peptide promotes activation of ROS-dependent cytotoxic functions and exerts immunomodulatory effects that enable an antiviral state in a dengue virus mouse model.General SignificanceThe increase of IFN-γ level and the differential modulation of antiviral proteins by the A233 peptide suggest that the molecule could activate an innate immune response with a possible further impact in the treatment of acute and chronic diseases.
Keywords:Comparative proteomics  Growth Hormone Secretagogue  ROS production  Antiviral activity
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