Lewis b 抗原 (Leb) 是一種存在於胃上皮細胞的表面抗原，它和幽門桿菌黏附因子blood group antigen-binding adhesin (BabA) 的結合有利於幽門桿菌貼附在胃粘膜上面。近年來，人們發現sialyl-Lewis x 抗原 (sLex)會表現在被幽門桿菌感染所引起的慢性發炎的胃上皮組織，而且此抗原可以作為幽門桿菌的sialic acid- binding adhesin (SabA)黏附因子的接受器。此外在那些不會表現Leb抗原的病人胃部裡，sLex抗原和幽門桿菌SabA黏附因子的結合會增加細菌在胃裡的菌落數目。sLex抗原是屬於Lewis histo-blood group antigen家族的一員，而且它的合成必須要經由2,3- sialyltransferases (ST3Gal) 和 1,3-fucosyltransferases (FUT)這兩種酵素催化才能完成。本篇研究的目的在於了解幽門桿菌能否誘發胃上皮組織表現sLex抗原以及幽門桿菌是透過什麼機制去影響胃上皮組織表現sLex抗原。為了要研究幽門桿菌感染如何去誘發胃上皮組織表現sLex抗原，我們建立了一個細胞模式來觀察。首先我們把人類胃上皮細胞株MKN45細胞和幽門桿菌一起培養,發現在幽門桿菌的刺激之下並不會誘使MKN45細胞的細胞膜表面表現sLex抗原，但在幽門桿菌感染細胞的培養過濾液刺激之下則會使MKN45細胞在48小時內持續增加sLex抗原的表現量。而且我們比較幽門桿菌感染細胞的培養過濾液和幽門桿菌的培養過濾液兩者誘導MKN45細胞表現sLex抗原的能力，後者誘導MKN45細胞表現sLex抗原量比前者少了17%。因此我們推測在幽門桿菌感染細胞的培養過濾液中除了細菌分泌出來的成分之外，細胞在感染時所釋放出的因子也會參與在調控sLex抗原表現的機制，不過細菌的分泌物在調控sLex抗原表現的部份是扮演比較重要的角色。另外我們的實驗結果也顯示出MKN45細胞在重組的人類TNF-或IL-8刺激之下並不會增加sLex抗原的表現量，可是一些幽門桿菌的致病因子，例如CagA、VacA、BabA可能會參與調控sLex抗原的表現，因為我們發現不論是CagA或VacA或BabA突變株誘導細胞表現sLex抗原的能力都比野生株差。此外在RT-PCR和real-time RT-PCR的分析結果顯示出在幽門桿菌培養過濾液的作用之下會增加細胞內 ST3Gal III和 FUT III、V、VI、VII mRNA表現量。我們的ST3Gal III 的promoter報導基因(reporter gene)分析結果指出在轉錄起始點(transcriptional start site)上游-123到-90 bp的這段區域可能具有正向調控的功能，而 FUT III promoter報導基因的分析結果也指出正向調控的區域可能座落在基因的-149到+32 bp的區域或者更下游的位置。總而言之，在本篇論文中我們發現幽門桿菌可以誘發胃上皮細胞表現sLex抗原，而且ST3Gal III和FUT III、V、VI、VII這五種基因與調控sLex抗原表現的機制有很大的關聯性。

Lewis b antigen (Leb) is a surface structure expressed on the gastric epithelium and interacts with blood group antigen-binding adhesin (BabA) of H. pylori, thus contributing to H. pylori adherence. Recently, sialyl-Lewis x antigen (sLex) has been found to be expressed on gastric epithelium during chronic inflammation induced by H. pylori and serves as a receptor for sialic acid-binding adhesin (SabA) of H. pylori. In patients who express no gastric Lewis b or weak Leb, the interaction between sLex and SabA increases the H. pylori colonization density. sLex is a member of Lewis histo-blood group antigen family and its biosynthesis is regulated by 2,3-sialyltransferases (ST3Gal) and 1,3-fucosyltransferases (FUT). Our aims of this study were to investigate whether and how H. pylori can trigger the sLex expression on gastric epithelium. In order to address these issues, we established a cell line model. We found that human gastric epithelial cell line MKN45 cells cocultured with H. pylori directly did not have detectable sLex antigen expression on cell surface. However, cells treated with H. pylori-infected cell filtrates or
H. pylori culture filtrates continued to increase sLex expression up to 48 h. By comparing the percentages of increased expression of sLex, we observed that cells treated with H. pylori culture filtrates consistently has 17% lower expression of sLex as compared to those treated with H. pylori-infected cell filtrates. These observations suggest that besides bacterial components secreted in the culture filtrates, factors released by cells in response to H. pylori infection are also involved in the up-regulation of sLex expression, although the former plays a predominant role. In this cell line model, sLex expression could not be induced to express on gastric epithelial cell line by recombinant human TNF- or IL-8 or their combination.
In contrast, certain virulence factors, such as CagA, VacA and BabA, they all participate in the up-regulation of sLex expression. This was shown by the fact that CagA, VacA, or BabA isogenic mutants all have reduced ability to induce sLex expression when compared to wild type. RT-PCR and real-time RT-PCR analysis indicated that enhanced expression of ST3Gal III and FUT III, V, VI and VII mRNA were observed in cells with increased sLex expression due to treatment with culture filtrates. ST3Gal III promoter reporter gene analysis indicated that -123 to -90 bp upstream of transcriptional start site may harbor positive regulatory elements involved in the up-regulation of sLex expression. FUT III promoter reporter gene analysis indicated that positive regulatory elements may be located within -149 to +32 bp region of FUT III gene or further downstream. In summary,
H. pylori can induce sLex expression on gastric epithelial cells and the ST3Gal III as well as FUT III, V, VI and VII genes are associated with the up-regulation of sLex
expression.

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