Role of the Exogenous HCV Core Protein in the Interaction of Human Hepatocyte Proliferation and Macrophage Sub-Populations 外源性hcv核心蛋白在人肝细胞增殖与巨噬细胞亚群相互作用中的作用.pdf

Role of the Exogenous HCV Core Protein in the Interaction of Human Hepatocyte Proliferation and Macrophage Sub-Populations Zhiyan Yao1,2., Xiaotian Song1,2., Shiru Cao1,2, Wenzhang Liang1,2, Wenran Lu1,2, Lijuan Yang1,2, Zhengzheng Zhang1,2, Lin Wei1,2* 1 Department of Immunology, Hebei Medical University, Shijiazhuang, China, 2 Key Laboratory of Immune mechanism and Intervention on Serious Disease in Hebei Province, Shijiazhuang, China Abstract Background: The core protein of hepatitis C virus (HCV) is found in the cytoplasm and nuclei of infected cells, including hepatocytes and other cells in the liver. The core protein could be secreted as well. Resident liver macrophages are dependent on the tissue micro-environment and external stimuli to differentiate M1 and M2 hypotypes with distinct functions, and increased expression of the nuclear transcription factor STAT3 was seen in M2-polarized macrophages. In contrast to proinflammatory M1 macrophages, M2 macrophages serve beneficial roles in chronic inflammation, immunosuppression, and tumorigenesis. Methods: Monocyte-derived human macrophage line (mTHP-1) was treated with the exogenous HCV core protein. Next, the mTHP-1 culture supernatant or cell pellets were added to culture media of normal human liver cell line (L02). Results: Only the culture supernatant stimulated L02 cells proliferation, which was associated with phosphorylated ERK expression. Core protein activated mTHP-1 cells showed enhanced pro- and anti-inflammatory cytokines secretion, which was accompanied by high expression of phosphorylated NF-kB105 and NF-kB65. However, phosphorylated STAT1, and STAT3, which are normally associated with M1 and M2 macrophage polarization, and cell surface expression of CD206, CD14, CD16, and CD86,