Wen Sicheng, Felley Christian P, Bouzourene Hanifa, Reimers Mark, Michetti Pierre, Pan-Hammarström Qiang
Department of Laboratory Medicine, Karolinska Institute at Huddinge Hospital, Stockholm, Sweden.
J Immunol. 2004 Feb 15;172(4):2595-606. doi: 10.4049/jimmunol.172.4.2595.
Helicobacter pylori infection is associated with an inflammatory response in the gastric mucosa, ultimately leading to cellular hyperproliferation and malignant transformation. Hitherto, only expression of a single gene, or a limited number of genes, has been investigated in infected patients. cDNA arrays were therefore used to establish the global pattern of gene expression in gastric tissue of healthy subjects and of H. pylori-infected patients. Two main gene expression profiles were identified based on cluster analysis. The data obtained suggest a strong involvement of selected Toll-like receptors, adhesion molecules, chemokines, and ILs in the mucosal response. This pattern is clearly different from that observed using gastric epithelial cell lines infected in vitro with H. pylori. The presence of a "Helicobacter-infection signature," i.e., a set of genes that are up-regulated in biopsies from H. pylori-infected patients, could be derived from this analysis. The genotype of the bacteria (presence of genes encoding cytotoxin-associated Ag, vacuolating cytotoxin, and blood group Ag-binding adhesin) was analyzed by PCR and shown to be associated with differential expression of a subset of genes, but not the general gene expression pattern. The expression data of the array hybridization was confirmed by quantitative real-time PCR assays. Future studies may help identify gene expression patterns predictive of complications of the infection.
幽门螺杆菌感染与胃黏膜的炎症反应相关，最终导致细胞过度增殖和恶性转化。迄今为止，仅对感染患者中单个基因或有限数量基因的表达进行了研究。因此，利用cDNA微阵列来确定健康受试者和幽门螺杆菌感染患者胃组织中的基因表达全局模式。基于聚类分析确定了两种主要的基因表达谱。获得的数据表明，特定的Toll样受体、黏附分子、趋化因子和白细胞介素在黏膜反应中发挥重要作用。这种模式与体外感染幽门螺杆菌的胃上皮细胞系所观察到的模式明显不同。通过该分析可得出“幽门螺杆菌感染特征”，即一组在幽门螺杆菌感染患者活检中上调的基因。通过聚合酶链反应分析细菌的基因型（编码细胞毒素相关抗原、空泡毒素和血型抗原结合黏附素的基因的存在情况），结果表明其与一部分基因的差异表达相关，但与一般基因表达模式无关。通过定量实时聚合酶链反应分析证实了微阵列杂交的表达数据。未来的研究可能有助于确定预测感染并发症的基因表达模式。
