Enhanced Expression of Interleukin-8 and Activation of Nuclear Factor Kappa-B in Endoscopy-negative Gastroesophageal Reflux Disease

Isomoto, Hajime; Saenko, Vladimir; Kanazawa, Yusei; Nishi, Yuki; Ohtsuru, Akira; Inoue, Kenichiro; Akazawa, Yuko; Takeshima, Fuminao; Omagari, Katsuhisa; Miyazaki, Masanobu; Mizuta, Yohei; Murata, Ikuo; Yamashita, Shunichi; Kohno, Shigeru

doi:10.1111/j.1572-0241.2004.04110.x

Cited by 85 publications

(72 citation statements)

References 31 publications

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“…These findings are further supported by increased activity of nuclear factor -light-chain-enhancer of activated B cells (NF-B) in the mucosa of GERD patients (55,81). NF-B is a ubiquitous transcription factor regulating proinflammatory responses.…”

Section: Inflammatory Mediators In the Inflamed Esophageal Mucosamentioning

confidence: 60%

“…In a Japanese study of patients with nonerosive reflux disease (NERD) with minimal mucosal involvement, as determined by endoscopy, IL-8 mRNA levels were increased compared with NERD patients with no mucosal involvement and with controls (63). After successful treatment with PPIs or Nissen fundoplication, IL-8 levels declined (55,83,138). High mucosal IL-8 levels predicted an increased relapse rate for GERD within 3 years, indicating a potential prognostic role for this cytokine (53).…”

Section: Inflammatory Mediators In the Inflamed Esophageal Mucosamentioning

confidence: 99%

“…IL-8 has been extensively studied in GERD and is expressed in high amounts in the affected mucosa of GERD patients (36,55,56,83,138). IL-8 is a powerful chemoattractant and activator of leukocytes and other nonimmune cells.…”

Section: Inflammatory Mediators In the Inflamed Esophageal Mucosamentioning

confidence: 99%

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Inflammatory mediators in gastroesophageal reflux disease: impact on esophageal motility, fibrosis, and carcinogenesis

Rieder

Biancani

Harnett

et al. 2010

American Journal of Physiology-Gastrointestinal and Liver Physi

114

102

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Gastroesophageal reflux disease (GERD) is one of the most common problems in clinical practice today. It is widely believed that functional and structural abnormalities of the gastroesophageal junction as well as an abnormal exposure to gastroduodenal contents are the main contributors to its pathogenesis. Novel findings of the inflammatory process in GERD suggest a far more complex process involving multifaceted inflammatory mechanisms. This review summarizes knowledge about the expression of inflammatory mediators in GERD and their potential cellular sources and provides an integrated concept of disease pathogenesis. In addition we evaluate the contribution of inflammatory mediators to well-known complications of GERD, namely motility abnormalities, fibrosis, and carcinogenesis. Novel findings regarding the pathophysiology of esophageal inflammation should enhance our understanding of GERD and its complications and provide new treatment insights.

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Section: Inflammatory Mediators In the Inflamed Esophageal Mucosamentioning

confidence: 60%

Section: Inflammatory Mediators In the Inflamed Esophageal Mucosamentioning

confidence: 99%

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Inflammatory mediators in gastroesophageal reflux disease: impact on esophageal motility, fibrosis, and carcinogenesis

Rieder

Biancani

Harnett

et al. 2010

American Journal of Physiology-Gastrointestinal and Liver Physi

114

102

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“…20 The relative IL-8 mRNA expression are significantly higher in esophageal mucosa of non-erosive reflux disease than controls, and lansoprazole treatment significantly reduces IL-8 mRNA expression levels. 21 However, no reports have described the relationship between circulating cytokines and reflux esophagitis, although several studies have shown the association between circulating cytokines and Barrett's esophagus. 22 In our study, circulating inflammatory cytokines such as IL-1, were increased in reflux esophagitis with adjusted analysis, even though its effect on reflux esophagitis was abolished with additional adjusted analysis for visceral fat and BMI.…”

mentioning

confidence: 99%

“…Several studies have suggested that mucosal cytokines are increased in GERD. 20,21 In 22 patients with non-erosive reflux disease, mucosal levels of cytokines (IL-8, IL-1, and CCL5) had a positive with recurrent reflux symptoms. 20 The relative IL-8 mRNA expression are significantly higher in esophageal mucosa of non-erosive reflux disease than controls, and lansoprazole treatment significantly reduces IL-8 mRNA expression levels.…”

mentioning

confidence: 99%

The Effect of Abdominal Visceral Fat, Circulating Inflammatory Cytokines, and Leptin Levels on Reflux Esophagitis

Nam

Choi

Ryu

et al. 2015

J Neurogastroenterol Motil

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Background/AimsAlthough adipocytes secrete inflammatory cytokines and adipokines, their role in reflux esophagitis is controversial. We investigated the association between visceral fat and inflammatory cytokines or adipokines in reflux esophagitis. MethodsAbdominal visceral fat and cytokines were measured in 66 individuals with reflux esophagitis and 66 age-and sex-matched controls. The mean values for visceral fat and cytokines were compared in cases and controls. Second, correlations between visceral fat and inflammatory cytokines were measured. Finally, multiple logistic regression models for odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the effects of visceral fat and cytokines on reflux esophagitis. ResultsVisceral fat, leptin, interleukin (IL)-6, and IL-1 were higher in reflux esophagitis compared to controls. Visceral fat showed a strong positive correlation with IL-6 (r = 0.523, P < 0.001), IL-8 (r = 0.395, P < 0.001), and IL-1 (r = 0.557, P < 0.001), and a negative correlation with adiponectin (r = −0.466, P < 0.001). With adjusted analysis, visceral fat/100 (OR, 4.32; 95% CI, 2.18-8.58; P < 0.001) and leptin (OR, 1.36; 95% CI, 1.10-1.69; P = 0.005) independently increased the risk of reflux esophagitis, but the effects of other cytokines were abolished.

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Reduction of Interleukin 8 Gene Expression in Reflux Esophagitis and Barrett's Esophagus With Antireflux Surgery

DeMeester²,

Vallböhmer³

et al. 2007

Arch Surg

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Hypothesis: Chronic inflammation of esophageal mucosa secondary to refluxed gastric juice increases gene expression of interleukin 8 (IL-8). Antireflux surgery can reduce this overexpression. Design: Prospective analysis of archival paraffinembedded tissue. Setting: Academic tertiary medical center. Patients and Methods: One hundred eight patients with reflux symptoms were classified according to pH monitoring and endoscopic and histologic findings. Twenty patients did not have reflux or mucosal injury; 47 had reflux disease (16 esophagitis and 31 Barrett's esophagus), 20 had dysplasia, and 21 had adenocarcinoma. Microdissection was performed to exclude inflammatory cells and stromal tissue. After RNA isolation and reverse transcription, IL-8 messenger RNA expression was measured using quantitative real-time polymerase chain reaction. All patients with reflux disease had Nissen fundoplication with biopsies at matched levels within the esophagus preoperation and postoperation. Results: Expression of IL-8 was increased in patients with reflux compared with those without reflux. Patients with the highest IL-8 expression were those with Barrett's dysplasia and adenocarcinoma (PϽ.001). In patients with reflux, Nissen fundoplication led to significantly decreased IL-8 expression compared with preoperative levels in esophagitis (P=.01) and Barrett's esophagus (P=.03). Conclusions: Interleukin 8 messenger RNA expression increases during the progression of reflux disease from normalsquamousmucosatoesophagealadenocarcinoma.Elimination of reflux with Nissen fundoplication significantly reduces IL-8 expression in both squamous and Barrett's mucosa. These results demonstrate that effective antireflux surgery can modulate the gene expression of esophageal mucosa and may impact the natural history of reflux disease.

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Enhanced Expression of Interleukin-8 and Activation of Nuclear Factor Kappa-B in Endoscopy-negative Gastroesophageal Reflux Disease

Abstract: Our results demonstrate enhanced mucosal expression of IL-8 in incipient GERD even without mucosal breaks. NF-kappaB activation may be implicated in the pathogenesis in GERD.

Cited by 85 publications

References 31 publications

Inflammatory mediators in gastroesophageal reflux disease: impact on esophageal motility, fibrosis, and carcinogenesis

Inflammatory mediators in gastroesophageal reflux disease: impact on esophageal motility, fibrosis, and carcinogenesis

The Effect of Abdominal Visceral Fat, Circulating Inflammatory Cytokines, and Leptin Levels on Reflux Esophagitis

Reduction of Interleukin 8 Gene Expression in Reflux Esophagitis and Barrett's Esophagus With Antireflux Surgery

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