المؤلفون: Shohreh Issazadeh-Navikas, Isaac Hurtado-Guerrero, José Pavia, María Jesús Pinto-Medel, Patricia Urbaneja, Natalia Mena-Vázquez, A. Alonso, Begoña Oliver-Martos, José Alcamí, Esther Calonge, Oscar Fernández, Laura Leyva, Antonio Alcami, Pablo Aliaga, Jose Luis Rodriguez-Bada, Bruno Hernáez

المساهمون: Instituto de Salud Carlos III, Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF), Regional Government of Andalusia (España), Red Española de Esclerosis Múltiple, Junta de Andalucía, European Commission

المصدر: Journal of Clinical Medicine
Volume 9
Issue 4
Digital.CSIC. Repositorio Institucional del CSIC
instname
Dipòsit Digital de la UB
Universidad de Barcelona
Journal of Clinical Medicine, Vol 9, Iss 959, p 959 (2020)
Hurtado-guerrero, I, Hernáez, B, Pinto-medel, M J, Calonge, E, Rodriguez-bada, J L, Urbaneja, P, Alonso, A, Mena-vázquez, N, Aliaga, P, Issazadeh-navikas, S, Pavia, J, Leyva, L, Alcamí, J, Alcamí, A, Fernández, Ó & Oliver-martos, B 2020, ' Antiviral, Immunomodulatory and Antiproliferative Activities of Recombinant Soluble IFNAR2 without IFN-ß Mediation ', Journal of Clinical Medicine, vol. 9, no. 4, pp. 959 . https://doi.org/10.3390/jcm9040959Test
Repisalud
Instituto de Salud Carlos III (ISCIII)

مصطلحات موضوعية: 0301 basic medicine, medicine.medical_treatment, soluble receptors, Cell, Immunology, lcsh:Medicine, Interferó, IFNAR, Pharmacology, Virus, Article, law.invention, immunology, 03 medical and health sciences, 0302 clinical medicine, Immune system, law, Interferon, medicine, Immunologia, Receptor, Soluble receptors, business.industry, lcsh:R, General Medicine, interferon, 030104 developmental biology, medicine.anatomical_structure, Cytokine, Recombinant DNA, Signal transduction, business, 030217 neurology & neurosurgery, medicine.drug

الوصف: Soluble receptors of cytokines are able to modify cytokine activities and therefore the immune system, and some have intrinsic biological activities without mediation from their cytokines. The soluble interferon beta (IFN-ß
) receptor is generated through alternative splicing of IFNAR2 and has both agonist and antagonist properties for IFN-ß
but its role is unknown. We previously demonstrated that a recombinant human soluble IFN-ß
receptor showed intrinsic therapeutic efficacy in a mouse model of multiple sclerosis. Here we evaluate the potential biological activities of recombinant sIFNAR2 without the mediation of IFN-ß
in human cells. Recombinant sIFNAR2 down-regulated the production of IL-17 and IFN-ɣ and reduced the cell proliferation rate. Moreover, it showed a strong antiviral activity, fully protecting the cell monolayer after being infected by the virus. Specific inhibitors completely abrogated the antiviral activity of IFN-ß
but not that of the recombinant sIFNAR2, and there was no activation of the JAK-STAT signaling pathway. Consequently, r-sIFNAR2 exerts immunomodulatory, antiproliferative and antiviral activities without IFN-ß
mediation, and could be a promising treatment against viral infections and immune-mediated diseases.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0674109f235fe62e9bedb2c4821b8dcbTest
https://hdl.handle.net/20.500.12105/9486Test

المؤلفون: Shohreh Issazadeh-Navikas, Ava Handley, Roger Pocock, Pedro Moreira, Sandeep Gopal, Camilla Nehammer, Huikyong Lee, Leelee Ng, Patrick Ejlerskov, David C. Rubinsztein

المساهمون: Handley, Ava [0000-0003-1543-1551], Rubinsztein, David C [0000-0001-5002-5263], Pocock, Roger [0000-0002-5515-3608], Apollo - University of Cambridge Repository

المصدر: eLife, Vol 8 (2019)
eLife
Nehammer, C, Ejlerskov, P, Gopal, S, Handley, A, Ng, L, Moreira, P, Lee, H, Issazadeh-Navikas, S, Rubinsztein, D C & Pocock, R 2019, ' Interferon-beta-induced miR-1 alleviates toxic protein accumulation by controlling autophagy ', eLife, vol. 8 . https://doi.org/10.7554/eLife.49930Test

مصطلحات موضوعية: 0301 basic medicine, medicine.medical_treatment, Protein aggregation, Mice, 0302 clinical medicine, Interferon, genetics, mammalian cells, Biology (General), 3' Untranslated Regions, Caenorhabditis elegans, Huntingtin Protein, biology, microRNA, Chemistry, General Neuroscience, GTPase-Activating Proteins, General Medicine, 3. Good health, Cell biology, Cytokine, C. elegans, Medicine, Research Article, medicine.drug, autophagy, QH301-705.5, Science, Chemical biology, chemical biology, General Biochemistry, Genetics and Molecular Biology, protein aggregation, Protein Aggregates, 03 medical and health sciences, Biochemistry and Chemical Biology, genomics, medicine, biochemistry, Animals, Humans, RNA, Messenger, Caenorhabditis elegans Proteins, Base Sequence, General Immunology and Microbiology, human cells, Autophagy, rab7 GTP-Binding Proteins, Genetics and Genomics, Interferon-beta, biology.organism_classification, MicroRNAs, 030104 developmental biology, rab GTP-Binding Proteins, Mutant Proteins, Rab, Peptides, 030217 neurology & neurosurgery, HeLa Cells

الوصف: Appropriate regulation of autophagy is crucial for clearing toxic proteins from cells. Defective autophagy results in accumulation of toxic protein aggregates that detrimentally affect cellular function and organismal survival. Here, we report that the microRNA miR-1 regulates the autophagy pathway through conserved targeting of the orthologous Tre-2/Bub2/CDC16 (TBC) Rab GTPase-activating proteins TBC-7 and TBC1D15 in Caenorhabditis elegans and mammalian cells, respectively. Loss of miR-1 causes TBC-7/TBC1D15 overexpression, leading to a block on autophagy. Further, we found that the cytokine interferon-β (IFN-β) can induce miR-1 expression in mammalian cells, reducing TBC1D15 levels, and safeguarding against proteotoxic challenges. Therefore, this work provides a potential therapeutic strategy for protein aggregation disorders.

وصف الملف: application/pdf; application/zip; text/xml

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::34810bf881501a7c32975e5884fc3cf7Test
https://elifesciences.org/articles/49930Test