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©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
Bone marrow-derived monocyte infusion improves hepatic fibrosis by decreasing osteopontin, TGF-β1, IL-13 and oxidative stress
Veruska Cintia Alexandrino de Souza, Thiago Almeida Pereira, Valéria Wanderley Teixeira, Helotonio Carvalho, Maria Carolina Accioly Brelaz de Castro, Carolline Guimarães D’assunção, Andréia Ferreira de Barros, Camila Lima Carvalho, Virgínia Maria Barros de Lorena, Vláudia Maria Assis Costa, Álvaro Aguiar Coelho Teixeira, Regina Celia Bressan Queiroz Figueiredo, Sheilla Andrade de Oliveira
Veruska Cintia Alexandrino de Souza, Andréia Ferreira de Barros, Camila Lima Carvalho, Virgínia Maria Barros de Lorena, Regina Celia Bressan Queiroz Figueiredo, Sheilla Andrade de Oliveira, Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, Recife, Pernambuco 50740-465, Brazil
Thiago Almeida Pereira, Immunopathogenesis Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, MD, USA and Laboratório de Doenças Parasitárias e infecciosas, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais 31270-901, Brazil
Valéria Wanderley Teixeira, Carolline Guimarães D’assunção, Álvaro Aguiar Coelho Teixeira, Departamento de Morfologia e Fisiologia Animal, Universidade Federal Rural de Pernambuco, Recife, Pernambuco 50740-465, Brazil
Helotonio Carvalho, Departamento de Biofísica e Radiobiologia, Universidade Federal de Pernambuco, Recife, Pernambuco 50740-465, Brazil
Maria Carolina Accioly Brelaz de Castro, Centro Acadêmico de Vitória, Universidade Federal de Pernambuco, Recife, Pernambuco 50740-465, Brazil
Vláudia Maria Assis Costa, Departamento de Medicina Tropical, Universidade Federal de Pernambuco, Recife 50740-465, Pernambuco, Brazil
Author contributions: de Souza VCA performed the majority of experiments, analyzed the data and wrote the paper; Carvalho CL and de Barros AF performed the immunologic investigations; D’Assunção CG participated in the treatment of animals; Pereira TA and Figueiredo RCBQ performed the immunohistochemistry assays; Carvalho H performed the biochemical investigations; Costa VMA, de Lorena VMB and de Castro MCAB performed the cellular isolation and characterization; Teixeira VW and Teixeira ÁAC performed the morphologic and morphometric investigations; de Oliveira SA designed and coordinated the research.
Supported by the Oswaldo Cruz Foundation (FIOCRUZ); the Pernambuco Science and Technology Support Foundation (FACEPE)(PROEP-FIOCRUZ 19/2015); the National Council of Technological and Scientific Development (CNPq) (Processes APQ 0906-2.11/08); the National Council for the Improvement of Higher Education (CAPES); and the Intramural Research Program of the National Institutes of Health (LPD/NIAID/NIH).
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Aggeu Magalhães Research Center (Protocol No. 15/2011).
Conflict-of-interest statement: The authors declare that they have no actual or potential conflicts of interest regarding this manuscript.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Sheilla Andrade de Oliveira, PhD, Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, Av. Professor Moraes Rego s/n, Cidade Universitária, Recife, Pernambuco 50740-465, Brazil.
sheilla@cpqam.fiocruz.br
Telephone: +55-81-21012581
Received: December 30, 2016
Peer-review started: January 4, 2017
First decision: February 9, 2017
Revised: February 22, 2017
Accepted: April 12, 2017
Article in press: April 12, 2017
Published online: July 28, 2017
Processing time: 209 Days and 9.3 Hours
AIM
To evaluate the therapeutic effects of bone marrow-derived CD11b+CD14+ monocytes in a murine model of chronic liver damage.
METHODS
Chronic liver damage was induced in C57BL/6 mice by administration of carbon tetrachloride and ethanol for 6 mo. Bone marrow-derived monocytes isolated by immunomagnetic separation were used for therapy. The cell transplantation effects were evaluated by morphometry, biochemical assessment, immunohistochemistry and enzyme-linked immunosorbent assay.
RESULTS
CD11b+CD14+ monocyte therapy significantly reduced liver fibrosis and increased hepatic glutathione levels. Levels of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-6 and IL-1β, in addition to pro-fibrotic factors, such as IL-13, transforming growth factor-β1 and tissue inhibitor of metalloproteinase-1 also decreased, while IL-10 and matrix metalloproteinase-9 increased in the monocyte-treated group. CD11b+CD14+ monocyte transplantation caused significant changes in the hepatic expression of α-smooth muscle actin and osteopontin.
CONCLUSION
Monocyte therapy is capable of bringing about improvement of liver fibrosis by reducing oxidative stress and inflammation, as well as increasing anti-fibrogenic factors.
Core tip: Chronic inflammation is now recognized as a central player in the development of liver fibrosis. Studies have shown that activated macrophages establish a link between chronic inflammation and fibrosis in various organs. The present study evaluated the therapeutic effects of bone marrow-derived CD11b+CD14+ monocytes in a murine model of liver damage. The results show that mice with transplants had improvement of liver fibrosis by way of a reduction in oxidative stress and inflammation and an increase in anti-fibrogenic factors. The study demonstrates the beneficial effects of cellular therapy in liver fibrosis and also reports on the important modulatory mechanisms involved.
