TNF and LTA gene polymorphisms reveal different risk in gastric and duodenal ulcer patients

Lanas, Ángel; García-González, María Asunción; Santolaria, Santos; Jb, Crusius; Mt, Serrano; Benito, Rafael; Peña, A. S.

doi:10.1038/sj.gene.6363798

Cited by 59 publications

(40 citation statements)

References 40 publications

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“…However, the differences in epithelial cytokine levels that we observed could not be explained by differences in cagA expression since all strains, i.e., those collected from both AS carriers and DU patients, were cagA positive. Various genetic host factors have been suggested to be of importance for the development of DUs (15,30). It is possible that the down-regulated epithelial cytokine levels that we observed in the DU patients in this study may be due to differences in genetic host factors.…”

Section: Vol 10 2003 Cytokines In H Pylori-infected Duodenum 121contrasting

confidence: 38%

Decreased Epithelial Cytokine Responses in the Duodenal Mucosa ofHelicobacter pylori-Infected Duodenal Ulcer Patients

Stromberg¹,

Edebo

Svennerholm³

et al. 2003

Clin Vaccine Immunol

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Helicobacter pylori colonizes the human stomach and areas of gastric metaplasia in the duodenum, but only a minority of those that are infected develop symptoms, e.g., peptic ulcers. Although most ulcers occur in the duodenum, almost all studies of mucosal immune responses against the infection have been limited to responses in the stomach. In the present study we evaluated whether there are differences in the levels of proinflammatory cytokines as well as immunoregulatory cytokines in the duodenal mucosa of duodenal ulcer (DU) patients and asymptomatic (AS) carriers which may be related to the development of duodenal ulcers. Duodenal biopsy specimens collected from normal mucosa as well as metaplastic mucosa of DU patients, AS carriers, and uninfected controls were analyzed for a number of cytokines by immunohistochemistry. Interestingly, the level of epithelial staining for several cytokines, e.g., interleukin-8 (IL-8), transforming growth factor ␤ (TGF-␤), and gamma interferon (IFN-␥), was found to be significantly lower in DU patients than in AS carriers and uninfected individuals. No differences were observed when cytokine staining in normal and metaplastic biopsy specimens was compared. However, larger numbers of IL-8-, IL-6-, TGF-␤-, and IFN-␥-positive mononuclear cells were observed in the duodenal lamina propria of both DU patients and AS carriers than in that of the uninfected controls. Our finding that a number of cytokines that may be important for the mucosal host defense against H. pylori are strongly decreased in the duodenal epithelium of ulcer patients suggests that a down-regulated immune response plays a role in the development of duodenal ulcers.

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Section: Vol 10 2003 Cytokines In H Pylori-infected Duodenum 121contrasting

confidence: 38%

Decreased Epithelial Cytokine Responses in the Duodenal Mucosa ofHelicobacter pylori-Infected Duodenal Ulcer Patients

Stromberg¹,

Edebo

Svennerholm³

et al. 2003

Clin Vaccine Immunol

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“…The haplotype containing the À307A allele has been associated with high TNF-a transcription rates. 19 Recently, an association between the polymorphic TNFA allele A at position À307 and gastric carcinoma has also been described in Caucasian populations by 2 different groups. 11,12 Although more severe gastric lesions have been demonstrated in patients simultaneously harboring virulent H. pylori strains and carrying the proinflammatory cytokine genotypes, 17,20 the assessment of each individual risk factor for gastric carcinoma in logistic models has not been evaluated yet.…”

mentioning

confidence: 98%

IL1RN polymorphic gene and cagA‐positive status independently increase the risk of noncardia gastric carcinoma

Rocha

Guerra

Rocha

et al. 2005

Intl Journal of Cancer

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Helicobacter pylori cagA-positive strains and host cytokine proinflammatory polymorphisms have been associated with gastric carcinoma. However, the individual role of each factor has not been evaluated yet. Our aim was to evaluate whether IL-1 gene cluster and tumor necrosis factor-a (TNFA)-307 polymorphisms, as well as cagA-positive status, are associated with gastric carcinoma in a non-Caucasian population by analyzing the data in logistic regression models. We evaluated 166 patients with noncardia gastric carcinoma and 541 blood donors. Among them, 702 were successfully genotyped for all cytokine studied: 166 with gastric carcinoma and 536 controls. The carcinoma patients were considered to be H. pylori-positive if culture alone or 2 among preformed urease test, stained smear or histologic section, serology, polymerase chain reaction (PCR) for ureA and urea breath test were positive. In blood donors, H. pylori status was based on enzyme-linked immunosorbent assay. The cagA status was determined by PCR or serology. IL1B-511/-31, IL1RN (interleukin-1 receptor antagonist) and TNFA-307 polymorphisms were genotyped by PCR, PCR with restriction fragment length polymorphism, or PCR with confronting 2-pair primers. We found that the IL1RN2 polymorphic allele (OR 5 1.93) was associated with noncardia gastric carcinoma, even after inclusion of age, gender and cagA status in the logistic models. However, the cagA-positive status was the strongest independent factor associated with gastric carcinoma (OR 5 11.89). The other polymorphisms were not significantly associated with the disease when they were evaluated in logistic models. This study provides evidence supporting the independent associations of cagA-positive H. pylori status and IL1RN polymorphisms with noncardia gastric carcinoma. ' 2005 Wiley-Liss, Inc.

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“…The following evidence supports this hypothesis: aspirin administration in rats results in an early increase in plasma TNF-␣ levels (Fiorucci et al, 1999), aspirin causes a time-and concentration-dependent increase in macrophage TNF-␣ mRNA expression and cytokine release (Fiorucci et al, 1998), gastric mucosal injury induced by aspirin administration or H. pylori infection results in TNF-␣-dependent induction of the apoptosis signaling cascade in gastric epithelial cells (Fiorucci et al, 1998), TNF-␣ exerts direct cytotoxic effects on gastric epithelium (Naito et al, 2001), and TNF-␣ gene polymorphisms are related to the development of peptic ulcers (Lanas et al, 2001) and infection with the H. pylori cagA subtype (Yea et al, 2001). However, the mechanism(s) involved in TNF-␣-induced CINC-1 production by gastric mucosa remains unclear.…”

mentioning

confidence: 99%

Tumor Necrosis Factor-α-Induced Cytokine-Induced Neutrophil Chemoattractant-1 (CINC-1) Production by Rat Gastric Epithelial Cells: Role of Reactive Oxygen Species and Nuclear Factor-κB

Handa

Naito²,

Takagi³

et al. 2004

J Pharmacol Exp Ther

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Rat cytokine-induced neutrophil chemoattractant-1 (CINC-1), a counterpart of the human growth-regulated oncogene product (GRO), has been suggested to participate in neutrophil recruitment in an experimental model of gastritis in rat. However, the mechanism(s) involved in regulation of CINC-1 production by the gastric mucosa remains unclear. The aim of this study was to investigate the mechanism(s) of CINC-1 production by rat gastric mucosa in vitro. All experiments were performed using rat normal gastric mucosal cell line (RGM-1). RGM-1s were stimulated with tumor necrosis factor (TNF)-␣, and CINC-1 mRNA levels (reverse transcription-polymerase chain reaction) and protein secretion (enzyme-linked immunosorbent assay) were assessed. The production of reactive oxygen species (ROS) and nuclear factor (NF)-B activation (translocation to the nuclei) in response to TNF-␣ stimulation was evaluated using fluorescence microscopy in the presence or absence of the inhibitors of mitochondrial electron flow and NF-B activation. Stimulation of RGM-1 cells with TNF-␣ resulted in an increase in intracellular oxidative stress, NF-B translocation to the nuclei, and up-regulation of CINC-1 mRNA and protein, which was prevented by interfering with mitochondria-dependent ROS production and NF-B activation. Taken together, these findings indicate that CINC-1, a counterpart of the human GRO, production by rat gastric epithelial cells in response to TNF-␣ stimulation is an oxidant stress-mediated and NF-Bdependent event.

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TNF and LTA gene polymorphisms reveal different risk in gastric and duodenal ulcer patients

Cited by 59 publications

References 40 publications

Decreased Epithelial Cytokine Responses in the Duodenal Mucosa ofHelicobacter pylori-Infected Duodenal Ulcer Patients

Decreased Epithelial Cytokine Responses in the Duodenal Mucosa ofHelicobacter pylori-Infected Duodenal Ulcer Patients

IL1RN polymorphic gene and cagA‐positive status independently increase the risk of noncardia gastric carcinoma

Tumor Necrosis Factor-α-Induced Cytokine-Induced Neutrophil Chemoattractant-1 (CINC-1) Production by Rat Gastric Epithelial Cells: Role of Reactive Oxygen Species and Nuclear Factor-κB

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