dc.contributor.author | Shintani, Y | en_US |
dc.contributor.author | Ito, T | en_US |
dc.contributor.author | Fields, L | en_US |
dc.contributor.author | Shiraishi, M | en_US |
dc.contributor.author | Ichihara, Y | en_US |
dc.contributor.author | Sato, N | en_US |
dc.contributor.author | Podaru, M | en_US |
dc.contributor.author | Kainuma, S | en_US |
dc.contributor.author | Tanaka, H | en_US |
dc.contributor.author | Suzuki, K | en_US |
dc.date.accessioned | 2017-07-17T10:50:21Z | |
dc.date.available | 2017-06-23 | en_US |
dc.date.issued | 2017-07-31 | en_US |
dc.date.submitted | 2017-06-23T12:57:57.357Z | |
dc.identifier.uri | http://qmro.qmul.ac.uk/xmlui/handle/123456789/24888 | |
dc.description.abstract | Recent research has shown that reparative (alternatively activated or M2) macrophages play a role in repair of damaged tissues, including the infarcted hearts. Administration of IL-4 is known to augment M2 macrophages. This translational study thus aimed to investigate whether IL-4 administration is useful for the treatment of myocardial infarction. Long-acting IL-4 complex (IL-4c; recombinant IL-4 mixed with anti-IL-4 monoclonal antibody as a stabilizer) was administered after coronary artery ligation in mice. It was observed that IL-4c administration increased accumulation of CD206+F4/80+ M2-like macrophages predominantly in the injured myocardium, compared to the control. Sorted cardiac M2-like macrophages highly expressed wide-ranging tissue repair-related genes. Indeed, IL-4c administration enhanced cardiac function in association with reduced infarct size and enhanced tissue repair (strengthened connective tissue formation, improved microvascular formation and attenuated cardiomyocyte hypertrophy). Experiments using Trib1 -/- mice that had a depleted ability to develop M2 macrophages and other in-vitro studies supported that these IL-4-mediated effects were induced via M2-like macrophages. On the other hand, when administered at Day 28 post-MI, the effects of IL-4c were diminished, suggesting a time-frame for IL-4 treatment to be effective. These data represent proof-of-concept of efficacy of IL-4 treatment for acute myocardial infarction, encouraging its further development. | en_US |
dc.description.sponsorship | This project was funded by the Heart Research UK Translational Research Grant
(RG2653/15/16), British Heart Foundation Programme Grant (RG/15/31236), and Queen
Mary Innovation Proof of Concept Grant (2015). The National Institute for Health Researchfunded
Barts Cardiovascular Biomedical Research Unit also supported this project. | en_US |
dc.description.sponsorship | This project was funded by the Heart Research UK Translational Research Grant (RG2653/15/16), British Heart Foundation Programme Grant (RG/15/31236), and Queen Mary Innovation Proof of Concept Grant (2015). The National Institute for Health Research-funded Barts Cardiovascular Biomedical Research Unit also supported this project. | |
dc.format.extent | 6877 - ? | en_US |
dc.language | eng | en_US |
dc.language.iso | en | en_US |
dc.relation.ispartof | Sci Rep | en_US |
dc.rights | Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. | |
dc.subject | Animals | en_US |
dc.subject | Cells, Cultured | en_US |
dc.subject | Interleukin-4 | en_US |
dc.subject | Intracellular Signaling Peptides and Proteins | en_US |
dc.subject | Macrophage Activation | en_US |
dc.subject | Macrophages | en_US |
dc.subject | Male | en_US |
dc.subject | Mice | en_US |
dc.subject | Mice, Inbred C57BL | en_US |
dc.subject | Myocardial Infarction | en_US |
dc.subject | Protein-Serine-Threonine Kinases | en_US |
dc.title | IL-4 as a Repurposed Biological Drug for Myocardial Infarction through Augmentation of Reparative Cardiac Macrophages: Proof-of-Concept Data in Mice. | en_US |
dc.type | Article | |
dc.rights.holder | © The Author(s), 2017. | |
dc.identifier.doi | 10.1038/s41598-017-07328-z | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/28761077 | en_US |
pubs.issue | 1 | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published online | en_US |
pubs.volume | 7 | en_US |
dcterms.dateAccepted | 2017-06-23 | en_US |