Role of Cytokines on the Progression of Liver Fibrosis in Mice Infected with Echinococcus multilocularis

Abstract

Fengming Tian,1,* Tao Jiang,2,* Xinwei Qi,3 Zhenyu Zhao,4 Bin Li,1 Madinaimu Aibibula,1 Hongyue Min,5 Jingyi Zhang,1 Yumei Liu,3 Xiumin Ma1,3,5 1State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Laboratory Center, Tumor Hospital Affiliated to Xinjiang Medical University, Urumqi, Xinjiang, 830011, People’s Republic of China; 2Animal Experiment Center, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830011, People’s Republic of China; 3State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830011, People’s Republic of China; 4School of Stomatology, Jilin University, Changchun, Jilin, 130021, People’s Republic of China; 5School of Basic Medicine, Xinjiang Medical University, Urumqi, Xinjiang, 830011, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiumin MaState Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Laboratory Center, Tumor Hospital Affiliated to Xinjiang Medical University, Urumqi, People’s Republic of ChinaEmail [email protected] LiuState Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, 830011, People’s Republic of ChinaEmail [email protected]: Liver fibrosis is a significant pathological change of Echinococcus multilocularis (E. multilocularis) infection. This study aimed to explore the role of cytokines on the progression of liver fibrosis in mice infected with E. multilocularis.Methods: Liver histopathological features at 2, 8, 30, 90 and 180 d were quantified by inflammatory severity score. The expression levels of inflammatory cytokines, fibrosis-related cytokines and hepatic cell apoptosis were measured using qRT-PCR and immunohistochemistry.Results: At the early stage of infection, parasite stimulation triggers the rapid recruitment of immune cells, such as macrophages and neutrophils. These infiltrated immune cells then produce a large number of cytokines, such as iNOS (inducible nitric oxide synthase), a pro-inflammatory cytokine; TGF-β (transforming growth factor) activated HSCs (hepatic stellate cells) to promote the proliferation of fibroblasts and secretion of ECM (extracellular matrix); MMP9 (matrix metalloproteinase 9) degraded basal ECM and facilitated its replacement by a highly dense interstitial matrix. At the middle and late stages of infection, the expression of IL-10 (interleukin-10) with general inhibitory effect was increased. The imbalance of fiber formation and degradation aggravated liver fibrosis. Meanwhile, the whole process of E. multilocularis infection was accompanied by the necrosis and apoptosis of hepatic cells.Conclusion: Along with the expansion of parasitic infection, dynamic changes in cytokine expression were observed on the liver fibrosis progression, which is helpful to provide some new ideas for the prevention and treatment of liver fibrosis in mice infected with E. multilocularis.Keywords: Echinococcus multilocularis, liver fibrosis, infection immunity, cytokines, parasite

Keywords

• echinococcus multilocularis
• liver fibrosis
• infection immunity
• cytokines
• parasite;