Brief Article
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World J Gastroenterol. Nov 21, 2011; 17(43): 4825-4830
Published online Nov 21, 2011. doi: 10.3748/wjg.v17.i43.4825
Effects of CpG-ODNs on phenotype and function of monocyte-derived dendritic cells in chronic hepatitis B
Xiao-Xing Xiang, Xia-Qiu Zhou, Jun-Xue Wang, Qing Xie, Xiong Cai, Hong Yu, Hui-Juan Zhou
Xiao-Xing Xiang, Department of Gastroenterology, Northern Jiangsu People’s Hospital, Medical College of Yangzhou University, Yangzhou 225001, Jiangsu Province, China
Xia-Qiu Zhou, Qing Xie, Hong Yu, Hui-Juan Zhou, Department of Infectious Disease, Rui jin Hospital, Medical College of Shanghai Jiao Tong University, Shanghai 200000, China
Jun-Xue Wang, Xiong Cai, Department of Infectious Disease, Changzheng Hospital, Second Military Medical University, Shanghai 200000, China
Author contributions: Xiang XX designed and performed the majority of the research, and wrote the paper; Zhou XQ, Xie Q, and Cai X contributed to the design, analysis, and financial support of the research; Wang JX, Yu H, and Zhou HJ performed some of the experiments, provided materials and reagents, and were involved in editing the manuscript.
Supported by Grants From Shanghai Committee of Science and Technology, Shanghai, China, No. 044119624
Correspondence to: Xiao-Xing Xiang, MD, Associate Professor of medicine, Department of Gastroenterology, Northern Jiangsu People’s Hospital, Medical College of Yangzhou University, 98 West Nantong Road of Yangzhou city, Yangzhou 225001, Jiangsu Province, China. xiangxx1965@yahoo.com.cn
Telephone: +86-514-87370315 Fax: +86-514-87937406
Received: February 27, 2011
Revised: June 21, 2011
Accepted: June 28, 2011
Published online: November 21, 2011
Abstract

AIM: 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.

CONCLUSION: 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.

Keywords: Chronic hepatitis B, Dendritic cell, CpG oligodeoxynucleotides, Hepatitis B surface antigen, Signal transduction