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

骨髓来源的单核细胞输注通过降低骨桥蛋白、TGF-β1、IL-13 和氧化应激改善肝纤维化

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作者: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 A

Aim

To evaluate the therapeutic effects of bone marrow-derived CD11b+CD14+ monocytes in a murine model of chronic liver damage.

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.

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.

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