title: NKG2D modulates aggravation of liver inflammation by activating NK cells in HBV infection.
abstract: Hepatitis B virus (HBV) infection is thought to be an immune-mediated liver disease. The mechanisms underlying natural killer (NK) cell group 2D receptor (NKG2D) that activates NK cells and participates in anti-HBV immunity and immunopathology has not been thoroughly elucidated. Peripheral NKG2D+and IFN-γ+NK cells frequencies and intrahepatic NKG2D and IFN-γ mRNA and protein expressions were determined in HBV-infected patients. Levels of NKG2D and IFN-γ mRNA and protein in NK cells, co-cultured with HBV-replicating HepG2 cells with or without NKG2D blockade, were analyzed. Serum and supernatant IFN-γ, TNF-α, perforin and granzyme B were measured. In results, peripheral NKG2D+and IFN-γ+NK cells frequencies, intrahepatic NKG2D and IFN-γ mRNA and protein levels, and serum IFN-γ, TNF-α, perforin and granzyme B levels were all highest in HBV-related acute-on-chronic liver failure group, followed by chronic hepatitis B and chronic HBV carrier groups. In vitro, NKG2D and IFN-γ mRNA and protein levels were higher in NK cells with IFN-α stimulation than without stimulation. Supernatant IFN-γ, TNF-α, perforin and granzyme B levels were increased under co-culture or IFN-α stimulating conditions, but were partially blocked by NKG2DmAb. In conclusion, NKG2D regulates immune inflammation and anti-viral response partly through activation of NK cells during HBV infection.
authors.affiliation: Department of Infectious Diseases, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Yadong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Infectious Diseases, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Infectious Diseases, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Shen
authors.affiliation: Department of Scientific Research, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Infectious Diseases, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Mingjing
authors.initials: M
authors.lastname: Jiao
authors.affiliation: Department of Infectious Diseases, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Weiyan
authors.initials: W
authors.lastname: Yu
authors.affiliation: Department of Infectious Diseases, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Hongzhu
authors.initials: H
authors.lastname: Yin
authors.affiliation: Department of Infectious Diseases, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Shang
authors.affiliation: Department of Infectious Diseases, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Qianfei
authors.initials: Q
authors.lastname: Liang
authors.affiliation: Department of Infectious Diseases, The Third Affiliated Hospital of Hebei Medical University, Shijiazhuang, China. zhaocy2005@163.com.
authors.forename: Caiyan
authors.initials: C
authors.lastname: Zhao
mesh_terms: D000328:Adult; D018920:Coculture Techniques; D018450:Disease Progression; D005260:Female; D053804:Granzymes / Q000097:blood; D056945:Hep G2 Cells; D006515:Hepatitis B virus / Q000276:immunology* / Q000502:physiology; D019694:Hepatitis B, Chronic / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000166:cytology* / Q000276:immunology; D008099:Liver / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000235:genetics* / Q000378:metabolism; D054353:Perforin / Q000097:blood; D011446:Prospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C573415:IFNG protein, human; C527085:KLRK1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D054353:Perforin; D007371:Interferon-gamma; D053804:Granzymes