The therapeutic effects of interleukin 10 gene-modified bone marrow-derived dendritic cells in a murine model of liver fibrosis
10.3760/cma.j.issn.0578-1426.2018.11.008
- VernacularTitle:白细胞介素10基因修饰的树突状细胞对肝纤维化小鼠的治疗作用及其机制
- Author:
Yejin XU
1
;
Xinyue TANG
;
Min YANG
;
Shengguo ZHANG
;
Minhui LIU
;
Yuxiang GUO
;
Mingqin LU
Author Information
1. 321000,浙江省金华市中心医院感染科
- Keywords:
Interleukin 10;
Dendritic cells;
Liver fibrosis;
Wnt/β-catenin signaling pathway;
Regulatory T cells
- From:
Chinese Journal of Internal Medicine
2018;57(11):835-840
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the therapeutic effects and mechanisms of interleukin-10 (IL-10) gene-modified dendritic cells (DC-IL-10) in mice with liver fibrosis. Methods DC-IL-10 was constructed in vitro, the phenotype and function of which were evaluated by flow cytometry. BALB/c mice were treated with intraperitoneal injection of carbon tetrachloride(CCl4)to establish liver fibrotic model. DC-IL-10 was administrated via tail vein. Animals were divided into 4 groups including normal dendritic cell (DC) control , liver fibrosis only, negative lentiviral transfection DC (DC-mock) and DC-IL-10. Liver function, cytokine secretion, T lymphocyte differentiation and liver histomorphology were tested. Real-time PCR and western blot were used to analyze the effect of DC-IL-10 on Wnt/β-catenin signaling pathway and its role in liver fibrosis. Results When compared with DC control and DC-mock, the expression of DC-IL-10 surface stimulating molecules (major histocompatibity complex-Ⅱ, CD80, CD86) were significantly decreased (F=14.708, 22.503, 12.595, respectively, all P<0.05), and DC-IL-10 significantly inhibited T lymphocyte proliferation (F=50.295, P<0.05). When compared with liver fibrosis group, serum alanine aminotransferase and aspartate transaminase were decreased in DC-IL-10 treated group (all P<0.05), other parameters including inflammatory factors (tumor necrosis factor α, IL-6, IL-1β) reduced (all P<0.05), the proportion of regulatory T cells (Treg) increased (F=6.742, P<0.05), pathological damage improved, the expression of Wnt3a, α-SMA and β-catenin mRNA and protein significantly reduced in DC-IL-10 treatment group(all P<0.001). Conclusions DC-IL-10 induces elevation of Treg for immune tolerance, as well as inhibition of inflammatory response, block of Wnt/β-catenin signaling pathway, which translates into improvement of liver fibrosis.
