CagA/cytotoxic strains of Helicobacter pylori and interleukin-8 in gastric epithelial cell lines.

Crabtree, Jean E.; Farmery, Susan M.; Lindley, I. J. D.; Figura, Natale; Peichl, P.; Tompkins, David

doi:10.1136/jcp.47.10.945

Cited by 311 publications

(217 citation statements)

References 39 publications

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“…The synthesis of proinflammatory cytokine IL-8 is strongly induced in gastric epithelial cells by infection with cag þ strains but not with cag ¹ strains (Crabtree et al, 1994;Sharma et al, 1995). We found that insertions in two ORFs [ORF13ؒ14 (VirB10 homologue) and ORF7 (no significant database match)] blocked IL-8 induction, as did deletion of the 19 kb cagII segment or of the entire cag PAI.…”

Section: Discussionmentioning

confidence: 99%

Analyses of the cag pathogenicity island of Helicobacter pylori

Akopyants¹,

Clifton²,

Kersulyte³

et al. 1998

Molecular Microbiology

677

331

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SummaryMost strains of Helicobacter pylori from patients with peptic ulcer disease or intestinal-type gastric cancer carry cagA, a gene that encodes an immunodominant protein of unknown function, whereas many of the strains from asymptomatically infected persons lack this gene. Recent studies showed that the cagA gene lies near the right end of a Ϸ37 kb DNA segment (a pathogenicity island, or PAI) that is unique to cagA þ strains and that the cag PAI was split in half by a transposable element insertion in the reference strain NCTC11638. In complementary experiments reported here, we also found the same cag PAI, and sequenced a 39 kb cosmid clone containing the left 'cagII' half of this PAI. Encoded in cagII were four proteins each with homology to four components of multiprotein complexes of Bordetella pertussis ('Ptl'), Agrobacterium tumefaciens ('Vir'), and conjugative plasmids ('Tra') that help deliver pertussis toxin and T (tumour inducing) and plasmid DNA, respectively, to target eukaryotic or prokaryotic cells, and also homologues of eukaryotic proteins that are involved in cytoskeletal structure. To the left of cagII in this cosmid were genes for homologues of HslU (heat-shock protein) and Era (essential GTPase); to the right of cagII were homologues of genes for a type I restriction endonuclease and ion transport functions. Deletion of the cag PAI had no effect on synthesis of the vacuolating cytotoxin, but this deletion and several cag insertion mutations blocked induction of synthesis of proinflammatory cytokine IL-8 in gastric epithelial cells. Comparisons among H. pylori strains indicated that cag PAI gene content and arrangement are rather well conserved. We also identified two genome rearrangements with end-points in the cag PAI. One, in reference strain NCTC11638, involved IS605, a recently described transposable element (as also found by others). Another rearrangement, in 3 of 10 strains tested (including type strain NCTC11637), separated the normally adjacent cagA and picA genes and did not involve IS605. Our results are discussed in terms of how cagencoded proteins might help trigger the damaging inflammatory responses in the gastric epithelium and possible contributions of DNA rearrangements to genome evolution.

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Section: Discussionmentioning

confidence: 99%

Analyses of the cag pathogenicity island of Helicobacter pylori

Akopyants¹,

Clifton²,

Kersulyte³

et al. 1998

Molecular Microbiology

677

331

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“…77,97,98 In addition, only type I strains were able to elicit secretion of Interleukin 8 (IL-8), which is the mediator of neutrophil migration by epithelial cells in vitro. 99,100 A number of epidemiological studies have shown that there is a strong correlation between infection with type I strains and occurrence of severe gastroduodenal diseases, whereas type II strains with attenuated virulence do not induce dramatic change in the gastric mucosa. 97,101 Thus, H. pylori strains that express CagA cause more extensive inflammation of the gastric mucosa, 99,100,102 and infections with these strains have been reported to be more likely to result in peptic ulceration, 97,98 atrophic gastritis 101 and gastric adenocarcinoma.…”

Section: Relevance Of Strain Types Of H Pylori In the Outcome Of Infmentioning

confidence: 99%

Helicobacter pylori: recent advances in the study of its pathogenicity and prevention

Aguilar¹,

Ayala²,

Fierros-Zarate³

2001

Salud pública Méx

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Helicobacter pylori has acquired great importance during the last two decades, after being recognized as an important pathogen that infects a great portion of the human population. This microorganism is recognized as the main causal agent of chronic gastritis and duodenal ulcers, and it is associated with the subsequent development of gastric carcinoma. The pathogenic mechanisms of H. pylori and their relation to gastric ailments have not been clearly defined. However, at present it is well established that urease, vacuolating cytotoxin VacA, and the pathogenicity island (cag PAI) gene products, are the main factors of virulence of this organism. Thus, individuals infected with strains that express these virulence factors probably develop a severe local inflammation that may induce the development of peptic ulcer and gastric cancer. The way the infection spreads throughout the world suggests the possibility that there are multiple pathways of transmission. Due to the importance that H. pylori has acquired as a human pathogen, laboratories worldwide are attempting to develop a vaccine that confers long-term immunological protection against infection by this microorganism. Hence, the objective of this review is to present the most relevant findings of the biology of H. Pylori and its interaction with the human host. The full version of this paper is available too at: http:// www.insp.mx/salud/index.html ResumenHelicobacter pylori ha adquirido gran importancia durante las últimas dos décadas, al ser reconocido como un importante patógeno que infecta una gran porción de la población humana. Este microrganismo es reconocido como el principal agente que causa la gastritis crónica y la úlcera duodenal, además de que se ha asociado con el subsecuente desarrollo del carcinoma gástrico. Los mecanismos patogé-nicos de H. pylori y su relación con los padecimientos gás-tricos no se han definido en forma clara. Sin embargo, actualmente está bien establecido que la ureasa, la citotoxina vacuolizante VacA y los productos de los genes de la isla de patogenicidad (cag PAI) son los principales factores de virulencia de este organismo. Así, los individuos infectados con cepas que expresan dichos factores de virulencia, probablemente manifiesten una marcada inflamación local que podría inducir el desarrollo de úlcera péptica y cáncer gástri-co. La manera como la infección se propaga a nivel mundial sugiere la posibilidad de múltiples vías de transmisión. A consecuencia de la importancia que H. pylori ha adquirido como patógeno humano, los laboratorios del mundo se esfuerzan para desarrollar una vacuna que confiera protección inmunológica de larga duración contra la infección por este microorganismo. El objetivo de esta revisión es presentar los hallazgos más relevantes sobre la biología de H. pylori y su interacción con su huésped humano. El texto completo de este artículo también está disponible en:

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“…It has been shown in vivo and in vitro (17,18) that H. pylori infection induces IL-1a, IL-1b, and IL-8, and that this process is independent of the expression of CagA, VacA, urease, or lipopolysaccharide (13,(19)(20)(21). The ability of H. pylori strains and mutants to induce IL-8 secretion from AGS cells is shown in Table 3.…”

Section: H Pylori Attachment To Cultured Gastric Epithelial Cellsmentioning

confidence: 99%

Induction of host signal transduction pathways by Helicobacter pylori

Segal

Lange

Covacci

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

189

153

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Adherence of Helicobacter pylori to cultured gastric epithelial cells is associated with several cellular events, including the tyrosine phosphorylation of a 145-kDa host protein; the reorganization of the host cell actin and associated cellular proteins, like vasodilator-stimulated phosphoprotein, adjacent to the attached bacterial cell; and the subsequent release of the cytokine, interleukin 8 (IL-8). H. pylori isolated from patients with ulcer disease and gastric cancer contain a DNA insertion, the cag pathogenicity island (PAI), that is not present in bacteria isolated from individuals with asymptomatic infection. Mutations in a number of PAI genes abolish tyrosine phosphorylation and IL-8 synthesis but not the cytoskeletal rearrangements. Kinase inhibition studies suggest there are two distinct pathways operative in stimulating IL-8 release from host cells and one of these H. pylori pathways is independent of the tyrosine phosphorylation step.

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CagA/cytotoxic strains of Helicobacter pylori and interleukin-8 in gastric epithelial cell lines.

Cited by 311 publications

References 39 publications

Analyses of the cag pathogenicity island of Helicobacter pylori

Analyses of the cag pathogenicity island of Helicobacter pylori

Helicobacter pylori: recent advances in the study of its pathogenicity and prevention

Induction of host signal transduction pathways by Helicobacter pylori

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