Effects of CpG-ODNs on phenotype and function of monocyte-derived dendritic cells in chronic hepatitis B  

作　　者：Xiao-Xing Xiang Xia-Qiu Zhou Jun-Xue Wang Qing Xie Xiong Cai Hong Yu Hui-Juan Zhou 

机构地区：[1]Department of Gastroenterology, Northern Jiangsu People＇s Hospital, Medical College of Yangzhou University, Yangzhou 225001, Jiangsu Province, China

出　　处：《World Journal of Gastroenterology》2011年第43期4825-4830,共6页世界胃肠病学杂志（英文版）

基　　金：Supported by Grants From Shanghai Committee of Scienceand Technology,Shanghai,China,No.044119624

摘　　要：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,CpGODNs/HBsAg,or tumor necrosis factor(TNF)-αfor 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.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,CpGODNs/HBsAg,or tumor necrosis factor（TNF）-αfor 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.

关 键 词：Chronic hepatitis B Dendritic cell CpG oligodeoxynucleotides Hepatitis B surface antigen Signal transduction 

分 类 号：Q78[生物学—分子生物学] S859.797[农业科学—临床兽医学]