title: WITHDRAWN: Natural Killer Cell Activating Receptor NKG2D Is Involved in the Immunosuppressant Effect of Mycophenolate Mofetil and Infection of Hepatitis B Virus.
abstract: In this study we investigated whether mycophenolate mofetil (MMF), a new immunosuppressant, and its metabolite mycophenolic acid (MPA) influence the activity of liver resident natural killer (NK) cells, resulting in increased susceptibility to hepatitis B virus (HBV) infection. We isolated the hepatic NK cells of C57BL/6 and C57BL/6JTgN (A1b1HBV) 44Bri) transgenic mice administered MMF in the presence or absence of interleukin (IL)-15, or incubated isolated hepatic NK cells in the presence or absence of MPA and used RT-PCR, immunolabeling to assess the expression of NK receptors Ly49A, NKG2A and NKG2D, and cytokine ELISA and [(3)H]-TdR-release assay to assess the activation and cytotoxic capacity of NK cells. After treatment of MMF in the presence or absence of IL-15, HBsAg titer was also measured in C57BL/6JTgN (A1b1HBV) 44Bri) transgenic mice. After both MPA and MMF treatments, NK cytotoxicity was reduced, NKG2D and Ly49A expression was down-regulated, but NKG2A was up-regulated. Down-regulation of NKG2D could be ameliorated by IL-15, and in HBV-transgenic mice, MMF treatment impaired NK cell activity, but did not influence virus replication, whereas IL-15 treatment depressed HBsAg titer. MPA and MMF mediate down-regulation of NKG2D in vitro and vivo, restricting the cytotoxic capacity of NK cells. Regulation of NKG2D may be important in the effect of immunosuppressant on NK cell activity and involved in HBV infection.
authors: Department of General Surgery, The First Affiliated Hospital, College of Medicine, ZheJiang University, HangZhou, China.
authors: S
authors: S
authors: Dong
authors: Department of General Surgery, The First Affiliated Hospital, College of Medicine, ZheJiang University, HangZhou, China.
authors: L
authors: L
authors: Geng
authors: Department of General Surgery, The First Affiliated Hospital, College of Medicine, ZheJiang University, HangZhou, China.
authors: M-D
authors: MD
authors: Shen
authors: Department of General Surgery, The First Affiliated Hospital, College of Medicine, ZheJiang University, HangZhou, China. Electronic address: medscids@126.com.
authors: S-S
authors: SS
authors: Zheng
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects*; D006509:Hepatitis B / Q000188:drug therapy* / Q000378:metabolism / Q000821:virology; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000096:biosynthesis*
chemical_list: D006514:Hepatitis B Surface Antigens; D007166:Immunosuppressive Agents; C527086:Klrk1 protein, mouse; D055655:NK Cell Lectin-Like Receptor Subfamily K; D009173:Mycophenolic Acid