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Comparison of virulence factors produced by Helicobacter pylori between Philippine and Thailand

菲律宾与泰国幽门螺杆菌毒力因子比较

基本信息

批准号：
18406015
负责人：
HIRAYAMA Toshiya
金额：
$ 9.74万
依托单位：
Nagasaki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18406015/
关键词：
Helicobacter pylori VacA Etiologic factors Bacterial toxin Cvtokine production Gene heterogeneity Pathoge nicitv Cell death 細菌由来病原因子ヘリコバクター多型比較調査フィリピンタイ PGE2

项目摘要

Although persistent infection by Helicobacter pylori is accepted as a major cause of gastroduodenal diseases, the cellular pathways responsible for the different outcomes such as peptic ulcer disease, gastric lymphoma, or gastric adenocarcinoma have not been defined. Variation in manifestations of H. pylori infection in different populations suggest effects of strains differing in virulence, or interactions involving the organism, environmental factor (s), and the host. Many H. pylori strains isolated from patients contain the cagA gene (cytotoxin-associated gene A)as well as produce the vacuolating cytotoxin, VacA. Additional H. pylori products, including urease, OipA, the neutrophil-activating protein NapA, adhesins, heat-shock protein, lipopolysaccharide, Bab, and IceA appear to be involved in virulence. In Philippine, Drs. Natividad and De Guzman proved that mosaicism in vacA alleles with two distinct families of vacA signal sequence (si and s2)and two distinct families of middle r … More egion alleles (ml and m2). And also cagA, iceA, and bab were investigated. The predominant vacA genotype is slbml (35%), slam 1 was found 29% of the biopsy samples. The cagA gene s detected in 53% of all the samples, 64% of gastric cancer biopsies are positive for cagA while in chronic gastritis only 50%. 41% of the camples are positive for ice A while for the bab gene the prevalent genotype is babAl (FwlRvl). However, in Thailand, we could not characterize and compare the same genes in clinical isolates from Thailand because of some technical proubles. Taken together, to know the relationship between the virulent genes and clinical outcome, we have to construct the functional research systems to detect the vacA genotypes and other status of cagA, iceA, and bab in Philippine and Thailand.During this investigation, we also characterized and compare the toxicity of m1VacA and m2VacA.In gastric cells, m1VacA stimulated COX-2 expression, followed by PGE2 production(Infection and Immunity 2007). In monocytes, mlVacA directly increases IL-8 production by activation of the p38 MAP kinase via intracellular Ca^<2+>-release, leading to activation of the transcription factors, ATF-2, CREB, and NF-kB. There is no difference in COX-2- and IL-8-productions between m1VacA and m2VacA(Journal of Immunology 2008).Furthermore, we are going to clarify the VacA toxicity in the presence of CagA. Less

虽然幽门螺杆菌的持续感染被认为是胃十二指肠疾病的主要原因，但导致消化性溃疡、胃淋巴瘤或胃腺癌等不同结局的细胞途径尚未确定。H.不同人群中的幽门螺杆菌感染表明菌株的毒力不同，或涉及生物体、环境因素和宿主的相互作用。许多H.从患者分离的幽门螺杆菌菌株含有cagA基因（细胞毒素相关基因A），并产生空泡化细胞毒素VacA。另一个H。幽门螺杆菌的产物，包括尿素酶、OipA、嗜酸性粒细胞活化蛋白NapA、粘附素、热休克蛋白、脂多糖、Bab和IceA，似乎与毒力有关。在菲律宾，Natividad和De Guzman博士证明了具有两个不同的vacA信号序列家族（s1和s2）和两个不同的中间序列家族的vacA等位基因的嵌合现象， ...更多信息区域等位基因（ml和m2）。同时对cagA、iceA和bab进行了研究。vacA基因型以slbml为主（35%），slam1占29%。cagA基因的检出率为53%，胃癌组织中cagA阳性率为64%，而慢性胃炎组织中cagA阳性率仅为50%。41%的样本为ice A阳性，而bab基因的流行基因型为babAl（FwIRvl）。然而，在泰国，由于一些技术问题，我们不能表征和比较来自泰国的临床分离株中的相同基因。因此，为了了解毒力基因与临床预后的关系，我们必须建立功能研究体系，检测菲律宾和泰国的vacA基因型和cagA、iceA和bab的其他状态。在本研究中，我们还表征和比较了m1 VacA和m2 VacA的毒性。在胃细胞中，m1 VacA刺激考克斯-2表达，其次是PGE2的产生（Infection and Immunity 2007）。在单核细胞中，mlVacA通过胞内Ca ^<2 +>-释放激活p38 MAP激酶，导致转录因子ATF-2、CREB和NF-κ B的激活，从而直接增加IL-8的产生。在m1 VacA和m2 VacA之间，考克斯-2-和IL-8-的产生没有差异（Journal of Immunology 2008）。少