摘要
探讨固有免疫分子DC-SIGN在幽门螺杆菌(H.pylori)感染的胃上皮细胞表达,及其与胃黏膜损伤的关系。选取经胃镜及组织病理检查确诊的72例慢性胃炎患儿胃黏膜活检标本,采用免疫组化检测胃黏膜上皮细胞DC-SIGN表达。体外建立幽门螺杆菌感染胃上皮细胞模型,采用流式细胞术检测幽门螺杆菌刺激的胃上皮细胞DC-SIGN以及CD80、CD86表达;ELISA测定胃上皮细胞与CD4+T细胞共培养后上清中IFN-γ、IL-4的含量。结果显示,慢性胃炎患者胃黏膜上皮细胞可见DC-SIGN表达,其中幽门螺杆菌感染阳性患者显高于阴性者(P<0.01),并随胃黏膜炎症程度加重DC-SIGN表达增强(P<0.01),显示与幽门螺杆菌感染明显相关(P<0.01)。此外发现,幽门螺杆菌体外可刺激胃上皮细胞上调表达DC-SIGN、CD86,且经幽门螺杆菌处理的胃上皮细胞可诱导CD4+T细胞IFN-γ分泌增多(P<0.01);经抗DC-SIGN单抗干预,可抑制DC-SIGN并相应下调CD86表达,且IFN-γ分泌减少及IFN-γ/IL-4比值下降(P<0.01、P<0.05)。结果表明,幽门螺杆菌感染的胃黏膜上皮细胞也表达树突状细胞(DC)表型DC-SIGN,并具有诱导T细胞向Th1分化为主的DC样细胞功能;DC-SIGN可能在介导胃上皮细胞于幽门螺杆菌胃黏膜损伤机制中发挥重要作用。
To explore the expression of dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin（DC-SIGN）on gastric epithelial cell during H.pylori infection and its possible immunomodulatory effects in the pathology of gastric mucosal lesion.The expression of DC-SIGN on gastric epithelial cells was examined by immunohistochemistry in 72 gastric mucosal biopsies of patients with chronic gastritis confirmed by upper endoscopy and histology.In vitro,the expressions of DC-SIGN,CD80 and CD86 on gastric epithelial（GES-1） with or without H.pylori infection were investigated by flow cytometry;and the ability of infected gastric epithelial cells to activate T cells was determined by mixed epithelial cell lymphocyte culture;The levels of IFN-γ and IL-4 in the cultural supernatant were detected by ELISA.The result showed that DC-SIGN was detectable in biopsies of patients with chronic gastritis,and higher expression of DC-SIGN was observed in biopsies from H.pylori infected patients（P0.01） or biopsies with more severe histological changes（P0.01）.We also found that the expression of DC-SIGN was positively correlated with H.pylori infection（P0.01）.Furthermore,the expressions of DC-SIGN and CD86 on GES-1 cells were up-regulated by H.pylori stimulation in vitro.H.pylori stimulated GES-1 cells were also capable of promoting IFN-γ secretion after co-cultured with CD4＋T cells（P0.01）.On the contrary,blockage of DC-SIGN with antibody significantly down-regulated the CD86 expression,decreased IFN-γ secretion（P0.01） and IFN-γ/IL-4 ratio（P0.05）.In summary,our study demonstrated that gastric epithelial cells were capable to express DC-SIGN which was originally identified on dendritic cells and promoting Th1 polarization.It is postulated that DC-SIGN probably plays an important role on gastric mucosal mediated by gastric epithelial cell during H.pylori infection.
出处
《现代免疫学》
CAS
CSCD
北大核心
2011年第2期101-106,共6页
Current Immunology
基金
国家自然科学基金资助项目(30770999
81000163)
上海市科委基础研究重点项目基金资助项目(09JC1409900)
关键词
幽门螺杆菌
胃黏膜炎症
胃上皮细胞
DC-SIGN
免疫调节
Helicobacter pylori
gastric mucosal inflammation
gastric epithelial cells
DC-SIGN
immunoregulation.
