title: Th1 and Th2 cytokine profiles induced by hepatitis C virus F protein in peripheral blood mononuclear cells from chronic hepatitis C patients.
abstract: Th1 and Th2 cytokine response has been confirmed to be correlated with the pathogenesis of HCV infection. The aim of the study is to investigate the Th1 and Th2 cytokine profiles induced by HCV alternate reading frame protein (F protein) in chronic hepatitis C patients. We assessed the immune responses specific to HCV F protein in 55 chronic HCV patients. IFN-γ, IL-2, IL-4 and IL-5 secretion by peripheral blood mononuclear cells (PBMC) post F protein stimulation were compared among HCV patients and healthy donors. Finally, the associations between HCV F protein and HLA class II alleles were explored. We found that the seroprevalence of anti-F antibodies in HCV-related hepatocellular carcinoma (HCC) patients was significantly higher than that of patients without HCC, but such a significant difference in humoral immune responses to F protein was not observed in HCV 1b-infected- and non-HCV 1b-infected-patients. Additionally, the PBMC proliferation of HCC patients was significantly lower than that of patients without HCC. Furthermore, F protein stimulation of PBMCs from F-seropositive patients resulted in Th2 biased cytokine responses (significantly decreased IFN-γ and/or IL-2 and significantly increased IL-4 and/or IL-5 levels) that reportedly may contribute to HCC progression and pathogenesis. However, no significant difference in the association between HCV F protein and HLA-DRB1*0201, 0301, 0405, 1001 and HLA-DQB1*0201, 0401, 0502, 0602 was observed in this study. These findings suggest that F protein may contribute to the HCV-associated bias in Th1/Th2 responses of chronic hepatitis C patients including the progress of HCC pathogenesis.
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, No. 24 Tongjiaxiang, Nanjing, Jiangsu Province, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Yue
authors.forename: Xiaozhao
authors.initials: X
authors.lastname: Deng
authors.forename: Xiangjun
authors.initials: X
authors.lastname: Zhai
authors.forename: Ke
authors.initials: K
authors.lastname: Xu
authors.forename: Jing
authors.initials: J
authors.lastname: Kong
authors.forename: Jinhai
authors.initials: J
authors.lastname: Zhang
authors.forename: Zhenxian
authors.initials: Z
authors.lastname: Zhou
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Yu
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Xu
authors.forename: Yunxi
authors.initials: Y
authors.lastname: Liu
authors.forename: Danyan
authors.initials: D
authors.lastname: Zhu
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D059866:HLA-DQ beta-Chains / Q000276:immunology; D059811:HLA-DRB1 Chains / Q000276:immunology; D016174:Hepacivirus / Q000276:immunology; D006508:Hepatitis Antibodies / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism; D007376:Interleukin-2 / Q000096:biosynthesis / Q000378:metabolism; D015847:Interleukin-4 / Q000096:biosynthesis / Q000378:metabolism; D015848:Interleukin-5 / Q000096:biosynthesis / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000821:virology; D008113:Liver Neoplasms / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D018417:Th1 Cells / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*; D014758:Viral Core Proteins / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism
chemical_list: D016207:Cytokines; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D059811:HLA-DRB1 Chains; D006508:Hepatitis Antibodies; D007376:Interleukin-2; D015848:Interleukin-5; D014758:Viral Core Proteins; C433031:hepatitis C protein F, Hepatitis C virus; D015847:Interleukin-4; D007371:Interferon-gamma
keywords: Alternate reading frame protein; CHC; ELISA; ELISPOT; F protein; HCC; HCV; HLA; Hepatitis C virus; Hepatocellular carcinoma; PBMC; PHA; SFC; SI; T helper; Th; Th1; Th2; alternate reading frame protein; chronic hepatitis C; enzyme-linked immunosorbent assay; enzyme-linked immunospot assay; hepatitis C virus; hepatocellular carcinoma; human leukocyte antigen; peripheral blood mononuclear cells; phytohemagglutinin; specific spot forming cells; stimulation index