| Research Abstract |
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
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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
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