幽门螺杆菌感染上调胃上皮细胞白细胞介素-18的产生。
Helicobacter pylori infection upregulates interleukin-18 production from gastric epithelial cells.
作者信息
Shimada Masaaki, Ando Takafumi, Peek Richard M, Watanabe Osamu, Ishiguro Kazuhiro, Maeda Osamu, Ishikawa Daisuke, Hasegawa Motofusa, Ina Kenji, Ohmiya Naoki, Niwa Yasumasa, Goto Hidemi
机构信息
Department of Gastroenterology, Nagoya University Graduate School of Medicine, Nagoya Memorial Hospital, Showa-ku, Nagoya, Japan.
出版信息
Eur J Gastroenterol Hepatol. 2008 Dec;20(12):1144-50. doi: 10.1097/MEG.0b013e32830edb15.
BACKGROUND
Helicobacter pylori infection induces a biased T helper type 1 (Th1) response that produces IFN-gamma and Fas ligand (FasL). Th1 cytokines are associated with apoptosis in the gastric epithelial cells.
AIM
We aimed to define the role of the recently cloned IL-18, a IFN-gamma inducing factor, in gastric mucosal injury induced by H. pylori infection.
METHODS
Twenty-seven gastric ulcer (GU) patients and 20 functional dyspepsia (FD) patients were enrolled in this study. Mucosal biopsy samples were obtained from the gastric antrum and GU site during endoscopy. Samples were used for histological examination, H. pylori culture and in-situ stimulation for 48 h in the presence of 10 microg/ml phytohemagglutinin-P. IL-18, IFN-gamma, and soluble FasL (sFasL) levels in culture supernatants were assayed by the enzyme-linked immunosorbent assay method. IL-18, IL-1beta-converting enzyme (ICE) and caspase-3 were evaluated by western blotting in gastric cancer cell lines (MKN45) cocultured with H. pylori.
RESULTS
All 27 GU patients and ten out of 20 FD patients were found to be H. pylori-positive, whereas ten FD patients were H. pylori-negative. Antral mucosal tissues from H. pylori-positive FD patients contained (P<0.01) higher levels of IL-18, IFN-gamma, and sFasL than those from uninfected FD patients. IL-18, IFN-gamma, and sFasL levels at the ulcer site were significantly (P<0.01) higher than those at distant sites in the antrum. A significant relationship was seen between IL-18 and IFN-gamma levels at the ulcer site (r=0.7, P<0.01). H. pylori eradication led to a significant decrease in the levels of IL-18, IFN-gamma, and sFasL at the ulcer site. Western blotting showed that IL-18, ICE, and caspase-3 were activated in gastric cancer cell lines cocultured with H. pylori.
CONCLUSION
This study suggests that H. pylori infection enhanced mucosal injury by stimulating a Th1 response, which was mediated by IL-18 upregulation as well as activation of ICE and caspase-3.
背景
幽门螺杆菌感染可诱导产生干扰素-γ和Fas配体（FasL）的偏向性1型辅助性T细胞（Th1）反应。Th1细胞因子与胃上皮细胞凋亡相关。
目的
我们旨在确定最近克隆的白细胞介素-18（IL-18），一种干扰素-γ诱导因子，在幽门螺杆菌感染诱导的胃黏膜损伤中的作用。
方法
本研究纳入了27例胃溃疡（GU）患者和20例功能性消化不良（FD）患者。在内镜检查期间从胃窦和GU部位获取黏膜活检样本。样本用于组织学检查、幽门螺杆菌培养以及在存在10微克/毫升植物血凝素-P的情况下进行48小时的原位刺激。通过酶联免疫吸附测定法检测培养上清液中IL-18、干扰素-γ和可溶性FasL（sFasL）的水平。在与幽门螺杆菌共培养的胃癌细胞系（MKN45）中通过蛋白质印迹法评估IL-18、白细胞介素-1β转换酶（ICE）和半胱天冬酶-3。
结果
27例GU患者和20例FD患者中的10例被发现幽门螺杆菌阳性，而10例FD患者幽门螺杆菌阴性。幽门螺杆菌阳性FD患者的胃窦黏膜组织中IL-18、干扰素-γ和sFasL水平（P<0.01）高于未感染的FD患者。溃疡部位的IL-18、干扰素-γ和sFasL水平显著（P<0.01）高于胃窦远处部位。溃疡部位的IL-18和干扰素-γ水平之间存在显著相关性（r=0.7，P<0.01）。根除幽门螺杆菌导致溃疡部位的IL-18、干扰素-γ和sFasL水平显著降低。蛋白质印迹显示在与幽门螺杆菌共培养的胃癌细胞系中IL-18、ICE和半胱天冬酶-3被激活。
结论
本研究表明幽门螺杆菌感染通过刺激Th1反应增强黏膜损伤，这是由IL-18上调以及ICE和半胱天冬酶-3激活介导的。
Zotero 插件