The study of oral streptococcal pathogenicity of autoimmune hepatitis

口腔链球菌对自身免疫性肝炎的致病性研究

• 批准号: 21592387
• 负责人: HIROTA Kastuhiko
• 金额: $ 2.91万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21592387/
• 关键词: S. intermedius; 細胞溶解毒素; 胆管上皮細胞; アポトーシス; Ca^<2+>振動; NFAT; サイトカイン; カルシニューリン; 感染防御免疫; サイトカインバランス; Bio-plex測定法; THP-1; バランス異常; IL-10; S.intermedius; 自己免疫性肝疾患; 細菌毒素; 小胞体異常; gp210; BiP; ヌクレアポリン; 口腔レンサ球菌

In the present study we analyzed possible relationship between calcium oscillations and each phenomenon in order to find out the molecular mechanisms in ILY-induced bile duct epithelial cells. Intracellular free calcium was analyzed by performing calcium imaging analysis of Fura-2 loaded cells. Increased free calcium was initially detected in the nuclei of ILY-treated cells subsequently followed with markedly increase in ER area. Calcineurin inhibitor cyclosporine A prevented ILY-induced calcineurin/ NFAT1 activation, cell death, and calcium oscillations. ILY in concentration of 10-40 ng/ ml capable of inducing calcium oscillations, activation of calcineurin/ NFAT1 signalling pathway ; inactivation of PI3K/ AKT/ MTOR pathway, and caused ER stress disorder resulted non-apoptotic cell death in HuCCT1 cells.

本研究分析了ILY诱导胆管上皮细胞钙振荡与上述现象之间的可能关系，以探讨ILY诱导胆管上皮细胞钙振荡的分子机制。通过对加载Fura-2的细胞进行钙成像分析来分析细胞内游离钙。ILY处理细胞后，细胞核内游离钙含量增加，随后内质网面积明显增加。钙调磷酸酶抑制剂环孢素A阻止ILY诱导的钙调磷酸酶/NFAT 1激活，细胞死亡和钙振荡。浓度为10-40 ng/ ml的ILY能够诱导钙振荡，激活钙调磷酸酶/NFAT 1信号通路;灭活PI 3 K/ AKT/ MTOR通路，并引起ER应激障碍，导致HuCCT 1细胞中的非凋亡性细胞死亡。

项目成果

Intermedilysin による小胞体異常の分子機構の解明

阐明中间素引起内质网异常的分子机制

• 发表时间: 2010
• 作者: 鈴木大;et al.;弘田克彦
• 通讯作者: 弘田克彦

The effect of extracellular DNA on the development of Streptococcus intermedius biofilm

胞外DNA对中间链球菌生物膜发育的影响

• 发表时间: 2011
• 作者: Hirota K;et al;Nur Asikin
• 通讯作者: Nur Asikin

High incidence of Pseudomonas aeruginosa from oropharyngeal biofilm in cerebrovascular infarction patients with dysphagia

脑血管梗死吞咽困难患者口咽部生物膜铜绿假单胞菌发生率高

• 发表时间: 2010
• 期刊: CHEST (印刷中)
• 作者: 宮内知彦;他;Katsuhiko Hirota
• 通讯作者: Katsuhiko Hirota

Gene expression profiling of human monocytic THP-1 cells stimulated with extracellular Streptococcus intermedius histine-like DNA binding

胞外中间链球菌组氨酸样 DNA 结合刺激的人单核 THP-1 细胞的基因表达谱

• 发表时间: 2011
• 作者: Hirota K;et al
• 通讯作者: et al

Long-term bacterial exposure can trigger nonsuppurative destructive cholangitis associated with multifocal epithelial inflammation

• DOI: 10.1038/labinvest.2010.40
• 发表时间: 2010-04-01
• 期刊: LABORATORY INVESTIGATION
• 影响因子: 5
• 作者: Haruta, Ikuko;Kikuchi, Ken;Yagi, Junji
• 通讯作者: Yagi, Junji