title: Cytokines elevated in patients with HBV-related acute-on-chronic liver failure promote NK cell mediated cytotoxicity through TRAIL.
abstract: OBJECTIVE
  The role of NK cells on inducing liver injury in patients with HBV-related acute-on-chronic liver failure (HBV-ACLF) is not well understood. The aim of this study was to determine the cytotoxicity of tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-expressed NK cells from HBV-ACLF patients and facilitate a better understanding of the immune pathogenesis of HBV-ACLF.
  
  
  METHODS
  Peripheral blood samples were obtained from HBV-ACLF patients, mild chronic hepatitis B (CHB) patients and healthy controls (HC). Circulating NK cells phenotype was determined using flow cytometry. Serum cytokine concentrations were ascertained using the CBA Inflammation kit. Cell apoptosis was analyzed using the FITC-annexin V Apoptosis Detection Kit.
  
  
  RESULTS
  Peripheral NK cells from HBV-ACLF expressed higher levels of TRAIL than those from CHB and HC. Expression of TRAIL on NK cells was correlated positively with serum IL-6 and IL-8 concentrations in HBV-ACLF patients, which is further confirmed by cytokines stimulation in vitro. NK cells caused a significant increase of apoptotic hepatocytes, and further increased the frequency of apoptosis in IL-6 and IL8-stimulated hepatocytes; the apoptosis was then inhibited partially by an anti-TRAIL monoclonal antibody.
  
  
  CONCLUSIONS
  These results suggested that inflammation cytokines elevated in patients with HBV-ACLF may promote NK cell mediated cytotoxicity through TRAIL pathway.
authors: Liver Failure Treatment and Research Center, Beijing 302 Hospital, Beijing, China. Electronic address: wanzhihong302@163.com.
authors: Zhihong
authors: Z
authors: Wan
authors: Research and Technology Service Center, Beijing 302 Hospital, Beijing, China.
authors: Guoming
authors: G
authors: Xie
authors: Liver Failure Treatment and Research Center, Beijing 302 Hospital, Beijing, China.
authors: Yichen
authors: Y
authors: Wu
authors: Liver Failure Treatment and Research Center, Beijing 302 Hospital, Beijing, China.
authors: Fangfang
authors: F
authors: Liu
authors: Liver Failure Treatment and Research Center, Beijing 302 Hospital, Beijing, China.
authors: Shaojie
authors: S
authors: Xin
authors: Liver Failure Treatment and Research Center, Beijing 302 Hospital, Beijing, China.
authors: Shaoli
authors: S
authors: You
authors: Liver Failure Treatment and Research Center, Beijing 302 Hospital, Beijing, China.
authors: Honglin
authors: H
authors: Liu
authors: Liver Failure Treatment and Research Center, Beijing 302 Hospital, Beijing, China.
authors: Chen
authors: C
authors: Li
authors: Liver Failure Treatment and Research Center, Beijing 302 Hospital, Beijing, China.
authors: Dongze
authors: D
authors: Li
mesh_terms: D065290:Acute-On-Chronic Liver Failure / Q000097:blood* / Q000821:virology; D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis; D016022:Case-Control Studies; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D005260:Female; D019694:Hepatitis B, Chronic / Q000097:blood* / Q000150:complications; D022781:Hepatocytes / Q000502:physiology; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000494:pharmacology; D016209:Interleukin-8 / Q000097:blood / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D015398:Signal Transduction; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000911:Antibodies, Monoclonal; D015850:Interleukin-6; D016209:Interleukin-8; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D020169:Caspases
keywords: Apoptosis; Hepatitis B virus; Inflammation; Tumor necrosis factor-related apoptosis-inducing ligand