Synthetic oligodeoxynucleotides inhibits IgE induction in human lymphocytes.

合成寡脱氧核苷酸可抑制人淋巴细胞中 IgE 的诱导。

• 批准号: 11671675
• 负责人: FUJIEDA Shigeharu
• 金额: $ 2.5万
• 依托单位: Fukui Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671675/
• 关键词: oligodeoxynucleotides; CpG motif; IgE; MY-1; IFN-γ; IL-12; palindromic sequence; human B cells; 合成DNA; PBMC; IL-4; anti-CD40

Syhthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG motifs have the capacity to stimulate Th-1 responses in mice. Th-1 cytokines are known to act as down-regulators of IgE production. In this study we investigated whether synthetic ODNs inhibited IgE production in human PBMC from normal donors stimulated with interleukin-4 (IL-4) plus anti-CD40 monoclonal antibody (mAb) in vitro. Thirty-mer single-stranded ODNs were randomly selected from the cDNA encoding the MPB-70 of Mycobacterium bovis BCG.Two ODNs containing CGTACG or AAGGTT inhibited IgE production by human PBMC.When a portion of the sequence of the core or flanking oligonucleotides in the ODN containing CGTACG was substituted with other oligonucleotides, ODNs containing NACGTTCG or A/CTCGTTCG equences specifically inhibited the IgE production of human PBMC in vitro. The inhibition of IgE production by certain ODN was mediated by both IFNγ and IL-12, since the ODN-induced suppression was blocked by the addition of anti-IFNγ or anti-IL-12 mAb. Also, the ODNs inhibited the induction of the ε germ-line transcript by IL-4. Our findings indicate that the administration of synthetic ODNs appears to be a therapeutic candidate for the treatment of IgE-dependent allergic disease in humans.

含有未甲基化CpG基序的合成寡脱氧核苷酸（ODNs）具有刺激小鼠Th-1应答的能力。已知Th-1细胞因子作为IgE产生的下调因子。在这项研究中，我们调查是否合成ODNs抑制IgE的生产从正常供体的人PBMC与白细胞介素-4（IL-4）和抗CD 40单克隆抗体（mAb）在体外刺激。从牛分枝杆菌BCG的MPB-70基因cDNA中随机选取30个单链寡核苷酸序列，发现CGTACG和AAGGTT两种寡核苷酸序列均能抑制人PBMC产生IgE，当CGTACG的寡核苷酸序列中的核心或侧翼序列被其他寡核苷酸取代时，NACGTTCG或A/CTCGTTCG序列的寡核苷酸序列能特异性地抑制人PBMC产生IgE。IFNγ和IL-12均能抑制ODN诱导的IgE产生，而抗IFN γ和抗IL-12单抗则能阻断ODN诱导的IgE产生。此外，ODNs抑制IL-4对ε生殖系转录本的诱导。我们的研究结果表明，合成ODNs的管理似乎是一个治疗的候选人IgE依赖性过敏性疾病的治疗。

项目成果

藤枝重治 他: "結核菌DNAおよび合成単鎖DNAによるIgE産生抑制の試み."日本鼻科学会誌. 38. 84-90 (1999)

Shigeharu Fujieda 等人：“尝试使用结核分枝杆菌 DNA 和合成单链 DNA 抑制 IgE 的产生。”日本鼻学会杂志 38. 84-90 (1999)。

Fujieda, S., Iho, S., Kimura, Y., Yamamoto, H., Igawa, H., Saito, H.: "Synthetic oligodeoxynucleotides inhibit IgE induction in human lymphocytes."Am.J.Respir.Crit.Care Med.. 162. 232-239 (2000)

Fujieda, S.、Iho, S.、Kimura, Y.、Yamamoto, H.、Ikawa, H.、Saito, H.：“合成寡脱氧核苷酸抑制人类淋巴细胞中的 IgE 诱导。”Am.J.Respir.Crit.Care

Fujieda, S.: "Induction of IgE class switching in the nasal mucosa."Allergology. 9. 532-538 (2000)

Fujieda, S.：“鼻粘膜中 IgE 类别转换的诱导。”过敏学。

藤枝重治 他: "合成DNAによるIgE産生抑制の機序."耳鼻免疫アレルギー. 17. 176-177 (1999)

Shigeharu Fujieda 等人：“合成 DNA 抑制 IgE 产生的机制”，17. 176-177 (1999)。

Fujieda, S., Saito, H., Iho, S., Yamamoto, S.: "DNA from mycobacterium bovis (BCG) and oligonucleotides suppressed IgE production by human lymphocytes : preliminary study."Jpn.J.Rhinol.. 38. 84-90 (1999)

Fujieda, S.、Saito, H.、Iho, S.、Yamamoto, S.：“牛分枝杆菌 (BCG) 的 DNA 和寡核苷酸抑制人类淋巴细胞产生 IgE：初步研究。”Jpn.J.Rhinol.. 38。