Department of Gastroenterology, Northern Jiangsu People's Hospital, Medical College of Yangzhou University, Yangzhou 225001, Jiangsu Province, China.
World J Gastroenterol. 2011 Nov 21;17(43):4825-30. doi: 10.3748/wjg.v17.i43.4825.
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).
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.
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.
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.
研究合成非甲基化 CpG 寡脱氧核苷酸（CpG-ODNs）单独或与重组乙型肝炎表面抗原（HBsAg）多肽联合应用对慢性乙型肝炎（CHB）患者单核细胞来源树突状细胞（DC）表型、功能和细胞内信号通路的影响。
从 CHB 患者和健康志愿者中分离外周血单核细胞，用重组人粒细胞-巨噬细胞集落刺激因子和白细胞介素-4 诱导为树突状细胞。然后用 CpG-ODNs、CpG-ODNs/ HBsAg 或肿瘤坏死因子（TNF）-α处理 DC 18 小时。用流式细胞术检测 DC 表面分子 HLA-DR、CD86 和 CD1a 的表达，用 Western blot 检测信号转导和转录激活因子（STAT1、3、4、5、6）和细胞信号转导抑制因子（SOCS1、3）的表达。此外，还测定了 DC 刺激同种异体 T 淋巴细胞的能力和 DC 释放的白细胞介素-12p70 的量。
与载体对照组相比，CHB 患者来源的 DC 经 TNF-α、CpG-ODNs 或 CpG-ODNs/ HBsAg 处理后，HLA-DR 的表达明显增加，IL-12p70 的释放得到刺激，并且 DC 刺激同种异体 T 淋巴细胞的能力增强。STAT1/4/6 和 SOCS1/3 的表达上调，但 STAT3/5 的表达没有上调，这是由 TNF-α、CpG-ODNs 和 CpG-ODNs/ HBsAg 引起的。此外，只有 CpG-ODNs 和 HBsAg 同时存在时，CD1a 的表达才上调。
CpG-ODNs 单独或与 HBsAg 联合应用对 CHB 患者受损的 DC 表型和功能具有显著的刺激作用，可能通过调节 STAT1、4、6 和 SOCS1、3 的表达。
