title: Effects of CpG-ODNs on phenotype and function of monocyte-derived dendritic cells in chronic hepatitis B.
abstract: OBJECTIVE
  To study the effects of synthetic nonmethylated CpG-containing oligodeoxynucleotides (CpG-ODNs), either alone or combined with recombinant Hepatitis B surface antigen (HBsAg) polypeptide, on the phenotype, function, and intracellular signaling pathways of monocyte-derived dendritic cells (DCs) in patients with chronic hepatitis B (CHB).
  
  
  METHODS
  Peripheral blood monocytes isolated from CHB patients and healthy volunteers were induced to be dendritic cells by recombinant human granulocyte-monocyte colony stimulating factor and interleukin-4. The DCs were then treated with CpG-ODNs, CpG-ODNs/HBsAg, or tumor necrosis factor (TNF)-α for 18 h. The expression of surface molecules including HLA-DR, CD86, and CD1a in DCs were detected by flow cytometry, and the expression of signal transducers and activators of transcription (STAT1, 3, 4, 5, 6) and suppressors of cell signaling (SOCS1, 3) were determined by Western blotting assay. In addition, the capacity of DCs to stimulate allogeneic T lymphocytes and the amount of IL-12p70 released from DCs were measured.
  
  
  RESULTS
  In the DCs derived from patients with CHB, treatment with TNF-α, CpG-ODNs, or CpG-ODNs/HBsAg, as compared to the vector control, significantly increased the expression of HLA-DR, stimulated the release of IL-12p70, and enhanced the capacity of DCs to stimulate allogenic T lymphocytes. The expressions of STAT1/4/6 and SOCS1/3, but not STAT3/5, were upregulated by TNF-α, CpG-ODNs, and CpG-ODNs/HBsAg. In addition, the expression of CD1a was upregulated only in the presence of both CpG-ODNs and HBsAg.
  
  
  CONCLUSIONS
  The treatment with CpG-ODNs, either alone or combined with HBsAg, has a remarkable stimulatory effect on the impaired phenotype and function of DCs in CHB, possibly by regulating the expression of STAT1, 4, 6 and SOCS1, 3.
authors.affiliation: Department of Gastroenterology, Northern Jiangsu People's Hospital, Medical College of Yangzhou University, Yangzhou 225001, Jiangsu Province, China. xiangxx1965@yahoo.com.cn
authors.forename: Xiao-Xing
authors.initials: XX
authors.lastname: Xiang
authors.forename: Xia-Qiu
authors.initials: XQ
authors.lastname: Zhou
authors.forename: Jun-Xue
authors.initials: JX
authors.lastname: Wang
authors.forename: Qing
authors.initials: Q
authors.lastname: Xie
authors.forename: Xiong
authors.initials: X
authors.lastname: Cai
authors.forename: Hong
authors.initials: H
authors.lastname: Yu
authors.forename: Hui-Juan
authors.initials: HJ
authors.lastname: Zhou
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000328:Adult; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000378:metabolism; D019694:Hepatitis B, Chronic / Q000276:immunology*; D006801:Humans; D018664:Interleukin-12 / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology*; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D010641:Phenotype; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D050791:STAT Transcription Factors / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D006514:Hepatitis B Surface Antigens; D009838:Oligodeoxyribonucleotides; D011994:Recombinant Proteins; D050791:STAT Transcription Factors; D018664:Interleukin-12