Bone marrow-derived monocyte infusion improves hepatic fibrosis by decreasing osteopontin, TGF-β1, IL-13 and oxidative stress

• Published in: World journal of gastroenterology : WJG 2017-07, Vol.23 (28), p.5146-5157
• Main Authors: de Souza, Veruska Cintia Alexandrino, Pereira, Thiago Almeida, Teixeira, Valéria Wanderley, Carvalho, Helotonio, de Castro, Maria Carolina Accioly Brelaz, D'assunção, Carolline Guimarães, de Barros, Andréia Ferreira, Carvalho, Camila Lima, de Lorena, Virgínia Maria Barros, Costa, Vláudia Maria Assis, Teixeira, Álvaro Aguiar Coelho, Figueiredo, Regina Celia Bressan Queiroz, de Oliveira, Sheilla Andrade
• Format: Article
• Language: English
• Subjects: Actins - metabolism; Animals; Basic Study; Carbon Tetrachloride - toxicity; CD11b Antigen - metabolism; Cell Separation; Cell- and Tissue-Based Therapy - methods; Cytokines - metabolism; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Ethanol - toxicity; Flow Cytometry; Glutathione - metabolism; Humans; Immunohistochemistry; Lipopolysaccharide Receptors - metabolism; Liver - metabolism; Liver - pathology; Liver Cirrhosis - chemically induced; Liver Cirrhosis - pathology; Liver Cirrhosis - therapy; Male; Mice; Mice, Inbred C57BL; Monocytes - metabolism; Monocytes - transplantation; Osteopontin - metabolism; Oxidative Stress
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v23.i28.5146

To evaluate the therapeutic effects of bone marrow-derived CD11b CD14 monocytes in a murine model of chronic liver damage. 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. 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. Monocyte therapy is capable of bringing about improvement of liver fibrosis by reducing oxidative stress and inflammation, as well as increasing anti-fibrogenic factors.