The role of innate immunity in inflammatory bowel disease

先天免疫在炎症性肠病中的作用

• 批准号: 15390223
• 负责人: KOHGO Yutaka
• 金额: $ 9.15万
• 依托单位: Asahikawa Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15390223/
• 关键词: Inflammatory Bowel Disease; Antibacterial peptides; Innate immunity; Crohn's disease; Alpha-defensins; Himan defensin 5; 内因性抗菌ペプチド; 潰瘍性大腸炎; デフェンシン; 粘膜免疫; ディフェンシン; 病原体認識

The aim of this study was to determine the role of antibacterial peptides in normal and inflamed intestine, and explore a potential therapeutic option for inflammatory bowel disease through the regulation of innate immunity by recombinant defensins.As results, this study demonstrated that, 1) human defensin 5 (HD-5) mRNA and protein expressed in small intestinal crypts of healthy volunteers and patients with Crohn's disease (CD) and ulcerative colitis, 2) gene profiles of defensins and toll-like receptors in the patients with CD was different from that in healthy volunteers, 3) bactericidal activity of HD-5 derived from the patients with CD was attenuated compared with that of healthy volunteers, 4) whereas the amino acid sequence of proHD-5 extracted from the patients with CD, disulphide bridges of the HD-5 of some CD patients were disappeared, suggesting that the function of HD-5 was regulated by a post-translational modification in inflammatory bowel disease and 5) recombinant HD-5, which was stable for trypsins and proteases, improved the survival rate of mice treated with 4% dextran sodium sulfate-treated.In summary, this study provided an important role of HD-5 in innate immunity of normal and inflamed inteastine, and proposed a novel therapeutic option for inflammatory bowel disease, targeting the impaired innate immunity.

本研究的目的是确定抗菌肽在正常和炎症肠道中的作用，并通过重组防御素调节先天免疫来探索炎症性肠病的潜在治疗选择。结果，本研究表明，1）在健康志愿者和克罗恩病（CD）患者的小肠隐窝中表达的人防御素5（HD-5）mRNA和蛋白和溃疡性结肠炎，2）CD患者中防御素和Toll样受体的基因谱与健康志愿者中的不同，3）与健康志愿者相比，来自CD患者的HD-5的杀菌活性减弱，4）而从CD患者中提取的proHD-5的氨基酸序列，一些CD患者的HD-5的二硫桥消失，表明HD-5的功能在炎性肠病中受翻译后修饰调节，5）重组HD-5对胰蛋白酶和蛋白酶稳定，提高了用4%葡聚糖硫酸钠治疗的小鼠的存活率。该研究提供了HD-5在正常和炎症肠的先天免疫中的重要作用，并提出了针对受损的先天免疫的炎症性肠病的新的治疗选择。

项目成果

Upregulation of hepcidin by interleukin-1beta in human hepatoma cell lines.

在人肝癌细胞系中，白介素-1β 上调铁调素。

• 发表时间: 2005
• 期刊: Hepatol Res. 33
• 作者: Inamura J;et al.
• 通讯作者: et al.

Combined use of dendritic cells enhances specific antileukemia immunity by leukemia cell-derived heat shock protein 70 in a mouse model with minimal residual leukemia cells.

在具有最少残留白血病细胞的小鼠模型中，联合使用树突状细胞可增强白血病细胞衍生的热休克蛋白 70 的特异性抗白血病免疫力。

• 发表时间: 2006
• 期刊: Int J Hematol. 84(5)
• 作者: Iuchi Y;Kohgo Y;et al.
• 通讯作者: et al.

Expression of LL-37 by human gastric epithelial cells as a potential host defence Mechanism against Helicobacter pylori.

人胃上皮细胞表达 LL-37 作为对抗幽门螺杆菌的潜在宿主防御机制。

• 发表时间: 2003
• 期刊: Gastroenterology 125
• 作者: Hase K;Kohgo Y;et al.
• 通讯作者: et al.

自然免疫, マクロファージ・抗原提示細胞腸粘膜上皮におけるPaneth細胞の自然免疫機能と病原体認識機構.

先天免疫、巨噬细胞/抗原呈递细胞肠粘膜上皮潘氏细胞的先天免疫功能和病原体识别机制。

• 发表时间: 2004
• 期刊: Annual Review免疫 2005巻
• 作者: 綾部時芳;高後裕;他
• 通讯作者: 他

Mirza ZK et al.: "Gastric intestinal metaplasia as detected by a monoclonal antibody is highly associated with gastric adenocarcinoma."Gut. 52. 802-807 (2003)

Mirza ZK 等人：“单克隆抗体检测到的胃肠上皮化生与胃腺癌高度相关。”Gut。