Expression of Interleukin‐18, a Th1 Cytokine, in Human Gastric Mucosa Is Increased in<i>Helicobacter pylori</i>Infection

Tomita, Toshihiko; Jackson, Andrew M.; Hida, Nobuyuki; Hayat, Mumtaz; Dixon, M. F.; Shimoyama, Takashi; Axon, Anthony; Robinson, Philip A.; Crabtree, Jean E.

doi:10.1086/318541

Cited by 86 publications

(72 citation statements)

References 52 publications

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“…An increased IL-18 expression has been reported in human atherosclerotic plaques 100) , and animal models further support the proatherogenic role of IL-18 101) and beneficial effects of IL-18 inhibition on plaque progression and composition 102) . In particular, several epidemiologic studies have reported that H. pylori infection upregulates IL-18 production from human gastric epithelial cells and lamina propria mononuclear cells isolated from H. pylori-infected gastric mucosa [103][104][105] . Furthermore, the serum H. pylori-IgG level is positively correlated with the serum IL-18 level 81) , and the IL-18 level is influenced by CagA-positive H. pylori strains 106) .…”

Section: H Pylori and Endothelial Dysfunctionmentioning

confidence: 99%

Helicobacter pylori—An Infectious Risk Factor for Atherosclerosis?

Yang

Lü

2014

JAT

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Accumulating evidence implicates Helicobacter pylori (H. pylori) infection in the pathogenesis of certain diseases localized outside the stomach, particularly those characterized by persistent and lowgrade systematic inflammation. Recently, the role of H. pylori infection in the development of atherosclerosis and its clinical complications has received attention. Atherosclerosis is a high-cost disease, and acute events resulting from this condition rank first among morbidity and mortality statistics in most industrialized countries. Atherosclerosis is a multifactorial disorder, and traditional risk factors explain only 50% of its etiology. Therefore, identifying new risk factors for atherosclerosis is necessary. Serological studies indicate that chronic H. pylori infection, especially that with more virulent strains, may predispose patients to the onset of atherosclerosis and related adverse clinical events, and PCR studies have detected H. pylori DNA in atherosclerotic plaques, although this finding remains controversial. If this association were to be confirmed, its importance to public health would be substantial, as the eradication of H. pylori is more straightforward and less costly than the longterm treatment of other risk factors. This review investigates the potential relationship between H. pylori infection and atherosclerosis from both epidemiological and pathogenic perspectives and characterizes the potential mechanisms underlying this correlation.

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Section: H Pylori and Endothelial Dysfunctionmentioning

confidence: 99%

Helicobacter pylori—An Infectious Risk Factor for Atherosclerosis?

Yang

Lü

2014

JAT

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“…Previous studies have shown that IL-18 is increased in different inflammatory conditions, such as Crohn's disease (37,38), rheumatoid arthritis (39), and leprosy (40). In Helicobacter-infected individuals, IL-18 mRNA expression was increased in the gastric mucosa (41,42). The serum IL-18 level was significantly increased in patients with gastric carcinoma, which is frequently found to be associated with H. pylori infection (2,43).…”

Section: Vaccine-induced Immunity Against Helicobacter Pylorimentioning

confidence: 99%

Vaccine-Induced Immunity againstHelicobacter pyloriInfection Is Impaired in IL-18-Deficient Mice

Akhiani

Schön

Lycke

2004

The Journal of Immunology

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Protective immunity against Helicobacter pylori infection in mice has been associated with a strong Th1 response, involving IL-12 as well as IFN-γ, but recent studies have also demonstrated prominent eosinophilic infiltration, possibly linked to local Th2 activity in the gastric mucosa. In this study we investigated the role of IL-18, because this cytokine has been found to be a coregulator of Th1 development as well as involved in Th2-type responses with local eotaxin production that could influence gastric eosinophilia and resistance to infection. We found that IL-18−/− mice failed to develop protection after oral immunization with H. pylori lysate and cholera toxin adjuvant, indicating an important role of IL-18 in protection. Well-protected C57BL/6 wild-type (WT) mice demonstrated substantial influx of CD4+ T cells and eosinophilic cells in the gastric mucosa, whereas IL-18−/− mice had less gastritis, few CD4+ T cells, and significantly reduced numbers of eosinophilic cells. T cells in well-protected WT mice produced increased levels of IFN-γ and IL-18 to recall Ag. By contrast, unprotected IL-18−/− mice exhibited significantly reduced gastric IFN-γ and specific IgG2a Ab levels. Despite differences in gastric eosinophilic cell infiltration, protected WT and unprotected IL-18−/− mice had comparable levels of local eotaxin, suggesting that IL-18 influences protection via Th1 development and IFN-γ production rather than through promoting local production of eotaxin and eosinophilic cell infiltration.

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“…Tomita et al (15) reported that antral IL-18 mRNA levels were up-regulated in H. pylori infection, whereas mature IL-18 protein was present in mucosa of both infected and uninfected subjects as measured by immunoblot analyses. In contrast, Fera et al reported that antral H. pylori infection was associated with IL-18 production as determined by immunohistochemistry; whereas IL-18 mRNA was expressed irrespective of H. pylori infection (16).…”

Section: T Hementioning

confidence: 99%

“…pylori strains containing an intact cag pathogenicity island (PAI) 4 , which encodes the type IV secretion system, and the outer inflammatory protein (OipA), which encodes the outer membrane protein, have been reported to increase the risk of more severe clinical outcomes (17,18). Tomita et al (15) reported that antral IL-18 mRNA levels were independent of the presence or absence of the cag PAI; however the relationship between OipA and IL-18 is not understood.…”

Section: T Hementioning

confidence: 99%

Regulation of IL-18 inHelicobacter pyloriInfection

Yamauchi

Choi

Lü

et al. 2008

The Journal of Immunology

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The gastric mucosal immune response is thought to be comprised predominantly of the Th1 type; however, there are limited data regarding the role of IL-18 in Helicobacter pylori-induced inflammation. We investigated IL-18 levels in gastric mucosal biopsy specimens as well as in isolated gastric epithelial cells and lamina propria mononuclear cells. We also investigated IL-18 levels in gastric epithelial cells and the monocyte cell line THP-1 cocultured with H. pylori. In both systems, IL-18 levels were markedly enhanced in H. pylori-infected epithelial cells and monocytes. IL-18 levels in H. pylori-infected gastric mucosa were well correlated with the severity of gastric inflammation, confirming that H. pylori-induced IL-18 plays an important role in gastric injury. Virulence factors of H. pylori; the cag pathogenicity island and OipA affected IL-18 induction in different manners. Up-regulation of IL-18 mRNA/protein in epithelial cells was dependent on both virulence factors. Interestingly, up-regulation of IL-18 mRNA in monocytes was independent of both factors, whereas IL-18 protein was OipA dependent – cag pathogenicity island independent, indicating that OipA regulates IL-18 induction in monocytes at the posttranscriptional level. IL-18 levels in the gastric biopsy specimens showed similar patterns to those in lamina propria mononuclear cells with respect to virulence factors, suggesting that submucosal monocytes/macrophages are the main source of IL-18 induced by H. pylori infection. H. pylori appeared to regulate the ERK/JNK→AP-1 pathway in both cell types. In addition, OipA and its related p38 pathway may be closely involved in IL-18 induction in H. pylori-infected gastric mucosa and may contribute to gastric injury.

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Expression of Interleukin‐18, a Th1 Cytokine, in Human Gastric Mucosa Is Increased inHelicobacter pyloriInfection

Cited by 86 publications

References 52 publications

Helicobacter pylori—An Infectious Risk Factor for Atherosclerosis?

Helicobacter pylori—An Infectious Risk Factor for Atherosclerosis?

Vaccine-Induced Immunity againstHelicobacter pyloriInfection Is Impaired in IL-18-Deficient Mice

Regulation of IL-18 inHelicobacter pyloriInfection

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